Neutrophils and macrophages: the main partners of phagocyte cell systems

Biological cellular systems are groups of cells sharing a set of characteristics, mainly key function and origin. Phagocytes are crucial in the host defense against microbial infection. The previously proposed phagocyte cell systems including the most recent and presently prevailing one, the mononuclear phagocyte system (MPS), grouped mononuclear cells but excluded neutrophils, creating an unacceptable situation. As neutrophils are archetypical phagocytes that must be members of comprehensive phagocyte systems, Silva recently proposed the creation of a myeloid phagocyte system (MYPS) that adds neutrophils to the MPS. The phagocytes grouped in the MYPS include the leukocytes neutrophils, inflammatory monocytes, macrophages, and immature myeloid DCs. Here the justifications behind the inclusion of neutrophils in a phagocyte system is expanded and the MYPS are further characterized as a group of dedicated phagocytic cells that function in an interacting and cooperative way in the host defense against microbial infection. Neutrophils and macrophages are considered the main arms of this system

Fraude Alimentar: fatores de risco e medidas de controlo e prevenção

A fraude alimentar é um tema de preocupação crescente para todos os intervenientes da cadeia alimentar. Ao nível da economia mundial, estima-se que a fraude alimentar tenha um custo anual global de 49 biliões de dólares e que 10% dos produtos alimentares que compramos estejam adulterados. A fraude alimentar baseia-se em atos intencionais por parte das empresas com a única motivação de gerar ganhos financeiros e não com o objetivo de causar prejuízos, ou denegrir a imagem da empresa alvo, característica que os distingue dos incidentes também intencionais do foro da Defesa Alimentar (Food Defence). Os atos de fraude alimentar podem incluir adulteração (substituição; diluição); falsa apresentação/rotulagem; contrafação; entre outros. Na maior parte dos casos não constituem um risco de segurança alimentar, tal como no caso da substituição da carne de vaca por carne de cavalo em 2013. Por outro lado, a utilização de adulterantes não convencionais, tem levado à deteção de fraudes devido ao impacto provocado em produtos distribuídos por vários países no mundo e por causarem graves repercussões na saúde pública, como é o caso da melamina no leite em 2008. Para as empresas, um incidente de fraude alimentar está associado a prejuízos significativos tais como: falência do negócio; destruição da imagem da marca; perda de credibilidade e redução do mercado entre outros e representa um fator de concorrência desleal entre produtores. A fraude alimentar ocorre geralmente quando a oportunidade para obter lucro é elevada e o risco de deteção da infração e as respetivas sanções são reduzidos. Os fatores que aumentam o risco de fraude alimentar bem como as oportunidades e a motivação dos fraudadores são: a globalização; as longas cadeias de abastecimento; o comércio através da Internet; a crise económica e os períodos de escassez de matérias-primas. A fraude normalmente incide em produtos de valor elevado ou que tenham muita procura e pouca oferta. Fatores como a criação de bases de dados partilhadas; a cooperação entre as várias autoridades oficiais; o aumento dos controlos ao longo da cadeia de abastecimento e na rastreabilidade dos produtos; o aumento das sanções; o desenvolvimento de métodos e tecnologia de autenticação; a introdução de metodologias de avaliação de vulnerabilidades e a criação de planos de mitigação na indústria são determinantes para a redução das oportunidades de fraude com vista à prevenção proativa da fraude alimentar e aumentar a confiança do consumidor na integridade dos alimentos que compra

Lipoarabinomannan, and its related glycolipids, induce divergent and opposing immune responses to Mycobacterium tuberculosis depending on structural diversity and experimental variations

Exposure to Mycobacterium tuberculosis (Mtb) may lead to active or latent tuberculosis, or clearance of Mtb, depending essentially on the quality of the host's immune response. This response is initiated through the interaction of Mtb cell wall surface components, mostly glycolipids, with cells of the innate immune system, particularly macrophages (Mfs) and dendritic cells (DCs). The way Mfs and DC alter their cytokine secretome, activate or inhibit different microbicidal mechanisms and present antigens and consequently trigger the T cell-mediated immune response impacts the host immune response against Mtb. Lipoarabinomannan (LAM) is one of the major cell wall components of Mtb. Mannosyl-capped LAM (ManLAM), and its related cell wall-associated types of glycolipids/lipoglycans, namely phosphatidylinositol mannosides (PIMs) and lipomannan (LM), exhibit important and distinct immunomodulatory properties. The structure, internal heterogeneity and abundance of these molecules vary between Mtb strains exhibiting distinct degrees of virulence. Thus ManLAM, LM and PIMs may be considered crucial Mtb-associated virulence factors in the pathogenesis of tuberculosis. Of particular relevance for this review, there is controversy about the specific immunomodulatory properties of these distinct glycolipids, particularly when tested as purified molecules in vitro. In addition to the variability in the glycolipid composition conflicting reports may also result from differences in the protocols used for glycolipid isolation and for in vitro experiments including immune cell types and procedures to generate them. Understanding the immunomodulatory properties of these cell wall glycolipids, how they differ between distinct Mtb strains, and how they influence the degree of Mtb virulence, is of utmost relevance to understand how the host mounts a protective or otherwise pathologic immune response. This is essential for the design of preventive strategies against tuberculosis. Thus, since clarifying the controversy on this matter is crucial we here review, summarize and discuss reported data from in vitro stimulation with the three major Mtb complex cell wall glycolipids (ManLAM, PIMs and LM) in an attempt to conciliate the conflicting findings.info:eu-repo/semantics/publishedVersio

Immunological hyporesponsiveness in tuberculosis: The role of mycobacterial glycolipids

Glycolipids constitute a major part of the cell envelope of Mycobacterium tuberculosis (Mtb). They are potent immunomodulatory molecules recognized by several immune receptors like pattern recognition receptors such as TLR2, DC-SIGN and Dectin-2 on antigen-presenting cells and by T cell receptors on T lymphocytes. The Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic relatives, phosphatidylinositol mannosides (PIMs) and lipomannan (LM), as well as other Mtb glycolipids, such as phenolic glycolipids and sulfoglycolipids have the ability to modulate the immune response, stimulating or inhibiting a pro-inflammatory response. We explore here the downmodulating effect of Mtb glycolipids. A great proportion of the studies used in vitro approaches although in vivo infection with Mtb might also lead to a dampening of myeloid cell and T cell responses to Mtb glycolipids. This dampened response has been explored ex vivo with immune cells from peripheral blood from Mtb-infected individuals and in mouse models of infection. In addition to the dampening of the immune response caused by Mtb glycolipids, we discuss the hyporesponse to Mtb glycolipids caused by prolonged Mtb infection and/or exposure to Mtb antigens. Hyporesponse to LAM has been observed in myeloid cells from individuals with active and latent tuberculosis (TB). For some myeloid subsets, this effect is stronger in latent versus active TB. Since the immune response in individuals with latent TB represents a more protective profile compared to the one in patients with active TB, this suggests that downmodulation of myeloid cell functions by Mtb glycolipids may be beneficial for the host and protect against active TB disease. The mechanisms of this downmodulation, including tolerance through epigenetic modifications, are only partly explored

Patterns of Mycobacterium tuberculosis-complex excretion and characterization of super-shedders in naturally-infected wild boar and red deer

Wild boar (Sus scrofa) and red deer (Cervus elaphus) are the main maintenance hosts for bovine tuberculosis (bTB) in continental Europe. Understanding Mycobacterium tuberculosis complex (MTC) excretion routes is crucial to define strategies to control bTB in free-ranging populations, nevertheless available information is scarce. Aiming at filling this gap, four different MTC excretion routes (oronasal, bronchial-alveolar, fecal and urinary) were investigated by molecular methods in naturally infected hunter-harvested wild boar and red deer. In addition MTC concentrations were estimated by the Most Probable Number method. MTC DNA was amplified in all types of excretion routes. MTC DNA was amplified in at least one excretion route from 83.0% (CI95 70.8-90.8) of wild ungulates with bTB-like lesions. Oronasal or bronchial-alveolar shedding were detected with higher frequency than fecal shedding (p 10(3) CFU/g or mL (referred here as super-shedders). Red deer have a significantly higher risk of being super-shedders compared to wild boar (OR = 11.8, CI95 2.3-60.2). The existence of super-shedders among the naturally infected population of wild boar and red deer is thus reported here for the first time and MTC DNA concentrations greater than the minimum infective doses were estimated in excretion samples from both species.We are grateful to all owners, hunters and hunting organizations that helped us to collect samples. Thanks are also due to Monica Cunha (INIAV, Portugal) for her advice during the setup of the laboratorial diagnosis techniques. Nuno Santos was supported by the Fundacao para a Ciencia e a Tecnologia (Ph.D. Grant SFRH/BD/69390/2010). This is also a contribution to MINECO Plan Nacional grant AGL2014-56305 and FEDER, and to the EU FP7 grant ANTIGONE # 278976

Visualization of CD4/CD8 T Cell Commitment

A system to innocuously visualize T cell lineage commitment is described. Using a “knock-in” approach, we have generated mice expressing a β-galactosidase reporter in place of CD4; expression of β-galactosidase in these animals appears to be an accurate and early indicator of CD4 gene transcription. We have exploited this knock-in line to trace CD4/CD8 lineage commitment in the thymus, avoiding important pitfalls of past experimental approaches. Our results argue in favor of a selective model of thymocyte commitment, demonstrating a fundamentally symmetrical process: engagement of either class of major histocompatibility complex (MHC) molecule by a differentiating CD4+CD8+ cell can give rise to T cell antigen receptor (TCR)hi thymocytes of either lineage. Key findings include (a) direct demonstration of a substantial number of CD4-committed, receptor/coreceptor-mismatched cells in MHC class II– deficient mice, a critical prediction of the selective model; (b) highly efficient rescue of such “mismatched” intermediates by forced expression of CD8 in a TCR transgenic line, and an explanation of why previous experiments of this nature were less successful—a major past criticism of the selective model; (c) direct demonstration of an analogous, though smaller, population of CD8-committed mismatched intermediates in class I–deficient animals. Finally, we found no evidence of a CD4 default pathway

Epidemiology of Mycobacterium bovis infection in wild boar (Sus scrofa) from Portugal

Tuberculosis has been diagnosed in wild boar (Sus scrofa) in several European countries during the last decade; however, almost no information has been reported to date for Portugal. This study aimed to investigate tuberculosis in wild boar in Portugal through characterization of Mycobacterium bovis infection and identification of disease risk factors. Tissue samples were obtained from hunted wild boar during the 2005 and 2006 hunting seasons. Samples were inspected for gross lesions and processed for culture. Acid-fast bacterial isolates were identified by polymerase chain reaction and spoligotyping. Associations between tuberculosis in wild boar and several variables linked to wild ungulate diversity and relative abundance, livestock density, and cattle tuberculosis incidence were investigated. Mycobacterium bovis isolates were identified in 18 of 162 wild boars from three of eight study areas. Infection rates ranged from 6% (95% confidence interval [CI(P95%)] = 1-21%) to 46% (CI(P95%) = 27-67%) in the three infected study areas; females in our sample were at greater risk of being infected than males (odds ratio = 4.33; CI(P95%) = 3.31-5.68). Spoligotyping grouped the M. bovis isolates in three clusters and one isolate was a novel spoligotype not previously reported in international databases. Detection of M. bovis was most consistently associated with variables linked to wild ungulate relative abundance, suggesting that these species, particularly the wild boar, might act as maintenance hosts in Portugal

The looming tide of nontuberculous mycobacterial infections in Portugal and Brazil

Nontuberculous mycobacteria (NTM) are widely disseminated in the environment and an emerging cause of infectious diseases worldwide. Their remarkable natural resistance to disinfectants and antibiotics and an ability to survive under low-nutrient conditions allows NTM to colonize and persist in man-made environments such as household and hospital water distribution systems. This overlap between human and NTM environments afforded new opportunities for human exposure, and for expression of their often neglected and underestimated pathogenic potential. Some risk factors predisposing to NTM disease have been identified and are mainly associated with immune fragilities of the human host. However, infections in apparently immunocompetent persons are also increasingly reported. The purpose of this review is to bring attention to this emerging health problem in Portugal and Brazil and to emphasize the urgent need for increased surveillance and more comprehensive epidemiological data in both countries, where such information is scarce and seriously thwarts the adoption of proper preventive strategies and therapeutic options.We acknowledge the support of FEDER through COMPETE and of National Funds through FCT - Fundacao para a Ciencia e a Tecnologia grants FCOMP-01-0124-FEDER-028359 [PTDC/BIA-MIC/2779/2012] and UID/NEU/04539/2013.info:eu-repo/semantics/publishedVersio

Interleukin-10: A Key Cytokine in Depression?

An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, namely, in depression. Of notice, recent studies showed that anti-inflammatory cytokines, such as IL-10, also modulate depressive-like behavior. In this article, we propose that the anti-inflammatory cytokine IL-10 is a putative link between two of the most widely reported phenomenon observed in depressed patients: the disruption of the hypothalamic-pituitary-adrenal axis and the imbalanced production of cytokines. If so, IL-10 might represent a novel target for antidepressant therapy

Microfluidic immunosensor for rapid and highly-sensitive salivary cortisol quantification

This paper presents a novel poly(dimethylsiloxane) (PDMS) microfluidic immunosensor that integrates a complementary metal-oxide-semiconductor (CMOS) optical detection system for a rapid and highly-sensitive quantification of salivary cortisol. The simple and non-invasive method of saliva sampling provides an interesting alternative to the blood, allowing a fast sampling at short intervals, relevant for many clinical diagnostic applications. The developed approach is based on the covalent immobilization of a coating antibody (Ab), a polyclonal anti-IgG, onto a treated PDMS surface. The coating Ab binds the capture Ab, an IgG specific for cortisol, allowing its correct orientation. Horseradish peroxidase (HRP)-labelled cortisol is added to compete with the cortisol in the sample, for the capture Ab binding sites. The HRP-labelled cortisol, bonded to the capture Ab, is measured through the HRP enzyme and the tetramethylbenzidine (TMB) substrate reaction. The cortisol quantification is performed by colorimetric detection of HRP-labelled cortisol, through optical absorption at 450 nm, using a CMOS silicon photodiode as the photodetector. Under the developed optimized conditions presented here, e.g., microfluidic channels geometry, immobilization method and immunoassay conditions, the immunosensor shows a linear range of detection between 0.01-20 ng/mL, a limit of detection (LOD) of 18 pg/mL and an analysis time of 35 min, featuring a great potential for point-of-care applications requiring continuous monitoring of the salivary cortisol levels during a circadian cycle.FCT with the reference project UID/EEA/04436/2013, by FEDER funds through the COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) with the reference project POCI-01-0145-FEDER-006941. V C Pinto thanks the FCT for the SFRH/BD/81526/2011 PhD grant. P J Sousa thanks the FCT for the SFRH/BD/81562/2011 PhD grant. S.O. Catarino thanks the FCT for the SFRH/BPD/108889/2015 grant, supported by national funds from Ministérios da Ciência, Tecnologia e Ensino Superior and by FSE through the POCH - Programa Operacional Capital Humanoinfo:eu-repo/semantics/publishedVersio