Respiratory antiviral immunity and immunobiotics: Beneficial effects on inflammation-coagulation interaction during influenza virus infection

Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation-coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.Fil: Zelaya, María Hortensia del Rosario. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; ArgentinaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina. Grupo de Investigación de Inmunobioticos; Argentin

Modulation of the immuno-coagulative response in a pneumococcal infection in malnourished mice nasally treated with Lactobacillus casei

We studied the systemic effects of the intranasal administration of Lactobacillus casei on the immuno-coagulative response in pneumoccocal infection in immunocompromised mice. Weaned mice consumed a protein-free diet (PFD) for 21 days and were therefore malnourished. Malnourished mice were fed a balanced conventional diet (BCD) for 7 days (BCD group) or a BCD for 7 days with nasal administration of viable L. casei on days 6 and 7 (BCD+LcN group). The malnourished control mice (MNC) received a PFD, whereas the well-nourished control mice (WNC) continually consumed a BCD. At the end of the treatment period, the mice were infected with Streptococcus pneumoniae. At different times after infection, we analysed the following parameters: global coagulation system, activation of coagulation, coagulation inhibitors, platelet count, leukocyte count and myeloperoxidase (MPO) activity, total proteins, albumin and acute phase proteins (APPs). The MNC group showed greater impairment in the coagulation tests and an increase in the positive APPs. These parameters were normalized by the L. casei treatment. However, the number of leukocytes, decreased by malnutrition, was improved only by the administration of L. casei. After infection, the BCD+LcN group showed similar results to those of the WNC group for most of the haemostatic parameters. The BCD+LcN group did not show significant variations in the prothrombin time or in the level of anticoagulant protein C, but showed higher levels of fibrinogen, platelets, albumin, leukocytes and MPO activity compared with the different experimental groups. The intranasal administration of L. casei was effective in modulating the pro-inflammatory aspects of coagulation without affecting coagulation itself.Fil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina;Fil: Laiño, Jonathan Emiliano. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina;Fil: Haro, Ana Cecilia. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina;Fil: Alvarez, Gladis Susana. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Agüero, Graciela. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Bioquimica Clinica Aplicada. Catedra de Bioquimica Clinica I; Argentina

Efecto de la leche humana sobre células de sangre y de médula ósea en un modelo de ratos desnutridos: estudio comparativo con leche de vaca

Estudios comparativos entre leche humana y leche de vaca para evaluar su impacto en la recuperación de las células de sangre y de médula ósea afectadas en ratones desnutridos.Comparative studies between human and cow milks in order to evaluate the impact of both milks on the recovery of blood and bone marrow cells affected in malnourished mice.Fil: García, Isabel Mercedes. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina; Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Patológica; Argentina;Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Zelaya, María Hortensia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Agüero, Graciela. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina

Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection

Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. Objective: the aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. Results: nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. Conclusions: the present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible to beneficially modulate the respiratory defenses against RSV by using heat-killed immunobiotics.Fil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japon;Fil: Chiba, Eriko. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japon;Fil: Zelaya, María Hortensia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Takahashi, Takuya. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japon;Fil: Tsukida, Koichiro. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japon;Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japon;Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina; Tohoku University. Graduate School of Agricultural Science. Food and Feed Immunology Group; Japon

Soluble factors from Lactobacillus reuteri CRL1098 have anti-inflammatory effects in acute lung injury induced by lipopolysaccharide in mice

We have previously demonstrated that Lactobacillus reuteri CRL1098 soluble factors were able to reduce TNF-a production by human peripheral blood mononuclear cells. The aims of this study were to determine whether L. reuteri CRL1098 soluble factors were able to modulate in vitro the inflammatory response triggered by LPS in murine macrophages, to gain insight into the molecular mechanisms involved in the immunoregulatory effect, and to evaluate in vivo its capacity to exert antiinflammatory actions in acute lung injury induced by LPS in mice. In vitro assays demonstrated that L. reuteri CRL1098 soluble factors significantly reduced the production of pro-inflammatory mediators (NO, COX-2, and Hsp70) and proinflammatory cytokines (TNF-a, and IL-6) caused by the stimulation of macrophages with LPS. NF-kB and PI3K inhibition by L. reuteri CRL1098 soluble factors contributed to these inhibitory effects. Inhibition of PI3K/Akt pathway and the diminished expression of CD14 could be involved in the immunoregulatory effect. In addition, our in vivo data proved that the PS induced secretion of the pro-inflammatory cytokines, inflammatory cells recruitment to the airways and inflammatory lung tissue damage were reduced in L. reuteri CRL1098 soluble factors treated mice, providing a new way to reduce excessive pulmonary inflammation.Fil: Griet, Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Zelaya, María Hortensia del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Mateos, Melina Valeria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Juarez, Guillermo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Font, Graciela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); ArgentinaFil: Rodriguez, Ana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentin

Lacticaseibacillus rhamnosus CRL1505 Peptidoglycan Modulates the Inflammation-Coagulation Response Triggered by Poly(I:C) in the Respiratory Tract

Lacticaseibacillus rhamnosus CRL1505 beneficially modulates the inflammation-coagulation response during respiratory viral infections. This study evaluated the capacity of the peptidoglycan obtained from the CRL1505 strain (PG-Lr1505) to modulate the immuno-coagulative response triggered by the viral pathogen-associated molecular pattern poly(I:C) in the respiratory tract. Adult BALB/c mice were nasally treated with PG-Lr1505 for two days. Treated and untreated control mice were then nasally challenged with poly(I:C). Mice received three doses of poly(I:C) with a 24 h rest period between each administration. The immuno-coagulative response was studied after the last administration of poly(I:C). The challenge with poly(I:C) significantly increased blood and respiratory pro-inflammatory mediators, decreased prothrombin activity (PT), and increased von Willebrand factor (vWF) levels in plasma. Furthermore, tissue factor (TF), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) expressions were increased in the lungs. PG-Lr1505-treated mice showed significant modulation of hemostatic parameters in plasma (PT in %, Control = 71.3 ± 3.8, PG-Lr1505 = 94.0 ± 4.0, p < 0.01) and lungs. Moreover, PG-Lr1505-treated mice demonstrated reduced TF in F4/80 cells from lungs, higher pro-inflammatory mediators, and increased IL-10 compared to poly(I:C) control mice (IL-10 in pg/mL, Control = 379.1 ± 12.1, PG-Lr1505 = 483.9 ± 11.3, p < 0.0001). These changes induced by PG-Lr1505 correlated with a significant reduction in lung tissue damage. Complementary in vitro studies using Raw 264.7 cells confirmed the beneficial effect of PG-Lr1505 on poly(I:C)-induced inflammation, since increased IL-10 expression, as well as reduced damage, production of inflammatory mediators, and hemostatic parameter expressions were observed. In addition, protease-activated receptor-1 (PAR1) activation in lungs and Raw 264.7 cells was observed after TLR3 stimulation, which was differentially modulated by PG-Lr1505. The peptidoglycan from L. rhamnosus CRL1505 is able to regulate inflammation, the procoagulant state, and PAR1 activation in mice and macrophages in the context of the activation of TLR3 signaling pathways, contributing to a beneficial modulation of inflammation-hemostasis crosstalk.Fil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Arellano Arriagada, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Fukuyama, Kohtaro. Tohoku University; JapónFil: Matsumoto, Kaho. Tohoku University; JapónFil: Marranzino, Gabriela. Universidad del Norte Santo Tomás de Aquino. Facultad de Ciencias de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Namai, Fu. Tohoku University; JapónFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Agüero, Graciela. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Kitazawa, Haruki. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentin

Immunobiotics and inflammation-coagulation

Probiotic lactic acid bacteria (LAB) strains can exert their beneficial effect on the host through their immunomudulatory activity and their anti-inflammatory properties. Although most research concerning the effect of probiotic lactobacilli on immune protection is focused on gastrointestinal tract pathogens, recent studies have centred on whether immunobiotics might sufficiently stimulate the common mucosal immune system to provide protection to other mucosal sites as well. On the other hand, increasing evidence points to an extensive cross-talk between inflammation and coagulation systems, whereby inflammation not only leads to activation of coagulation but coagulation also considerably affects inflammatory activity. In this chapter we focused on (i) the coagulation pathway, (ii) coagulation-inflammation interactions and specific coagulation abnormalities related to malnutrition and acute lung injury, and (iii) novel applications of immunobiotics in the inflammation-coagulation relationship. More specifically, in this chapter we reviewed the work of our laboratory on the use of immunobiotics to modulate the above relationship in immunocompetent and immunodeficient hosts. In our research, we demonstrated for the first time that a probiotic Lactobacillus casei CRL431 effectively regulated coagulation activation and fibrinolysis inhibition during respiratory infections, which led to a decrease in fibrin deposits in the lung of immunocompetent and immunocompromised mice. This protective effect of L. casei CRL431 was mediated by the induction of high levels of anti-inflammatory interleukins such as IL-4 and IL-10. These interleukins would contribute to regulate the pro-inflammatory, procoagulant and antifibrinolytic effects of TNF-alfa, IL-1 and IL-6 that were increased after the respiratory challenge. These findings can be useful to develop novel strategies using immunobiotics to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions. Diseases associated with high levels of PAI-1 such as cardiovascular disease, acute lung injury and acute respiratory distress syndrome could be targets of these novel therapeutic strategies. In addition, it is to be hoped that the knowledge gained in the unraveling of the coagulation and inflammation pathophysiology will result in further refinements and improved therapies for patients with severe systemic injuries and septic shock. However, much remains to be learnt about the cellular and molecular mechanisms involved in the interaction between mucosal immune system, inflammation, coagulation and immunobiotic LAB.Fil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Agüero, María Graciela. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentin

Tissue factor at the crossroad of coagulation and cell signaling

The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween its role in coagulation and cell signaling through thiol-disulfide exchange reactions in the context of physiologically relevant lipid microdomains. Inflammatory mediators, including reactive oxygen species, activators of the inflammasome, and the complement cascade play pivotal roles inTF procoagulant activation on monocytes, macrophages and endothelial cells. We furthermore discuss how TF, intracellular ligands, co-receptors, and associated proteases are integrated in PARdependent cell signaling pathways controlling innate immunity, cancer, and metabolic inflammation.Knowledge of the precise interactions of TF in coagulation and cell signaling is important for understanding effects of new anticoagulants beyond thrombosis and identification of new applications of these drugs for potential additional therapeutic benefits.Fil: Zelaya, María Hortensia del Rosario. Center For Thrombosis And Hemostasis Mainz (cth); Alemania. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clínica Aplicada; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Rothmeier, Andrea. The Scripps Research Institute; Estados UnidosFil: Ruf, Wolfram. Center For Thrombosis And Hemostasis Mainz (cth); Alemania. The Scripps Research Institute; Estados Unidos. German Center For Cardiovascular Research (dzhk); Alemani

Impacto de Lactobacillus rhamnosus CRL1505 sobre los mecanismos hemostáticos alterados durante la inmunosupresión experimental inducida por la ciclofosfamida

Different drugs used during cancer treatments can affect the hemostatic mechanisms. Previously, we demonstrated that lactic acid bacteria modulate effectively coagulation activation during respiratory infections. The aim of this work was to evaluate whether viable or non-viable Lactobacillus rhamnosus CRL1505 (Lr1505V or Lr1505NV) were able to modulate alterations on hemostatic mechanisms induced by cyclophosphamide (Cy), an antineoplastic drug used in several types of cancer.Adult Swiss-mice were orally treated with LrV or LrNV (108 CFU/d/mouse) during 5 consecutive days. On day 6, lactobacilli-treated and untreated control mice received one intraperitoneal dose of Cy (150 mg/kg). Cy only decreased prothrombin activity and platelet count, but the platelet count reached normal values at the end of the experiment. Considering that Cy did not induce significant alterations, we decided to study the effect of LrV or LrNV in an experimental pneumosepsis model in immunosuppressed host by Cy. At day 3 post Cy administration, the immunosuppressed mice were nasally infected with Streptococcus pneumoniae 6B (107 CFU/ml). Cy-treated mice showed increased susceptibility to infection and alterations in the immune-coagulative response. However, preventive administration of L. rhamnosus significantly reduced microbial counts in lung and blood, regulated TNF-α/IL-10 ratio in serum, and modulated hemostatic parameters with increase in prothrombin activity, normalization of platelet counts, and temporal increase of fibrinogen that act as acute phase protein. The results suggest that L. rhamnosus modulate immune-coagulative response during an early S. pneumoniae-infection in Cy-immunosuppressed mice. It would be necessary a later evaluation of the hemostatic parameters during the infection, and to study some specific marker of coagulation activation and/or fibrinolysis, as well as endothelial activation markers.Fil: Gramajo López, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentin

Immunomodulatory lactic acid bacteria in regulation of haemostatic alterations induced during a respiratory infection in immunosuppressed host by malnourishment. Basic mechanisms of action

Malnutrition induces a decrease in immunity that affects the ability of the organism to deal with an infectious challenge. The clotting system is considered a branch of immunity and its activation is important in the pathogenesis of an infectious disease. This work was conducted to determine coagulation modifications in malnourished hosts before and during infection. Weaned mice were malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed a balanced conventional diet. Malnourished mice (MN) and WNC were challenged intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL), and lung samples were taken at different times post infection. The results were that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung. Thus, an increase in thrombin antithrombin complexes (TATc) in plasma and BAL was observed. In the MN group, infection induced a rise in TATc in plasma and BAL and increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in activated protein C and antithrombin in BAL and an early decrease followed by an increase in plasma Factor VIII were also observed. Also MN demonstrated high levels of acute phase reactant and an increase in TNF-alfa. The feeding with a diet supplemented with Lactobacillus casei induced an anti-inflamatory cytokine pattern which contributed to limit coagulation activation and to normalize the regulatory protein. These findings will help to develop further strategies to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions. Key words: malnourishment, blood coagulation, plasma, bronchoalveolar lavage, coagulation activation, coagulation inhibitors, TAT complexes.Fil: Zelaya, María Hortensia del Rosario. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Laiño, Jonathan Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Haro, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; ArgentinaFil: Aguero Villoldo, Maria Graciela. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Clinica Aplicada. Cátedra de Bioquímica Clinica I; Argentin