Biochemical and functional properties of blood eosinophils from patients with the hypereosinophilic syndrome

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Protein deficiency during Trichinella spiralis infection impairs lung immunity against newborn larvae

The goal of this study was to analyse the effects of a protein-deficient (PD) diet on antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro against newborn larvae (NBL) of Trichinella spiralis in the lungs of infected rats. Two groups of weaning Wistar rats received a PD diet (6.5% casein) and other two received a control diet (C, 20% casein). After ten days, one group of each diet was infected (PDI and CI) with muscle larvae. Lung tissue extracts (LTE) and lung cell suspension (LCS) were obtained. PDI had lower titres of anti-NBL antibodies in LTE than CI. In ADCC assays using control cells, NBL mortality percentage was lower with LTE from PDI than LTE from CI (P <.01). In assays using control cytotoxic sera, ADCC was exerted by LCS from CI at all days post-infection (p.i.), but only by LCS from 13 days p.i. from PDI. ADCC assays combining LTE and LCS from the same group showed a lower response for PDI than for CI (P <.0001). LCS from PDI contained lower numbers of neutrophils, eosinophils and FcεRI+ cells than CI. PD may diminish ADCC activity against T spiralis NBL in lungs through alterations in specific antibodies and effector cells.Fil: Vila, Cecilia Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; ArgentinaFil: Saracino, María Priscila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; ArgentinaFil: Lombardo, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; ArgentinaFil: Falduto, Guido Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; ArgentinaFil: Díaz, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Calcagno, Marcela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; ArgentinaFil: Pallaro, Anabel Nora. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Sanidad Nutrición Bromatología y Toxicología; ArgentinaFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; Argentin

IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni

Eosinophil and Tissue-invasive Parasitic Helminth

Eosinophils are primarily tissue resident cells, and play important roles in host’s immune responses and maintenance of chronic infection during infection with tissue-invasive parasitic helminth. Such parasite secretes particular molecules to evade eosinophil-mediated helminthotoxicity. Continuous competition between eosinophil and parasite leads to stable equilibria between them. Recent evidence provides a concept that not only eosinophils contribute to parasite’s survival but also parasite modulates host’s immune response. Therefore, it is important to know complex interrelationship between eosinophil and parasite to understand how gently parasite talk to eosinophils and how carefully eosinophils listen to parasite’s voice. In this regard, this review examin papers about eosinophil-mediated tissue inflammatory responses in response to helminthic parasiteope

Inflammatory Responses of the Jird to Brugia Pahangi: Parasite Stage Specificity and Role of the Macrophage.

The host systemic and peritoneal inflammatory responses against different stages of Brugia pahangi were compared in intraperitoneally infected-jirds. Systemic inflammatory responses were assessed by measuring the pulmonary granulomatous response to B. pahangi antigen-coated beads (PGRN). Peritoneal inflammation was characterized by enumeration of different cell types in peritoneal exudates following infection. Further, the toxoplasmacidal activity and TNF-$\alpha$-like production of peritoneal macrophages were also characterized. Infection with L3, L4, male worms, female worms, microfilariae (MF) or dead adult worms induced a rapid PGRN. This response decreased to levels of controls in jirds inoculated with living parasites at the chronic time period, indicating that viable worms are needed to downmodulate the PGRN, but MF are not required. Large numbers of female worms induced greater downmodulation of the PGRN than low numbers, and adult worm infection resulted in greater downmodulation of the PGRN than MF inoculation. These observations suggest that parasite burden is important in filarial-induced PGRN decrease. The greatest peritoneal inflammatory response was found in infections that resulted in MF production, and this response did not correspond to the level of PGRN indicating that MF act as potent inflammatory stimulus when compartmentalization occurs. Gamma radiation inhibited the development and decreased the survival of B. pahangi L3. This effect was inversely related to the radiation dose used. Downmodulation of the PGRN occurred in infections with normal L3 or L3 irradiated with 15 krads, but not in infections of L3 irradiated with more than 15 krads, supporting the importance of the adult stage in the PGRN downmodulation in absence of MF. The PGRN decrease occurred at the time period when the molt to adult worms had just occurred, suggesting that larval stages are also involved in the downregulation phenomenon. Macrophages from jirds inoculated with male or female B. pahangi were activated to kill Toxoplasma at 15 DPI coinciding with the peak of PGRN. TNF production peaked at 56 DPI and decreased markedly at 135 DPI. Absence of toxoplasmacidal activity was found in macrophages after 56 DPI corresponding to PGRN decrease. These data suggest that filaria-specific hyporesponsiveness may be associated with a downmodulation of macrophage function.* ftn*Originally published in DAI Volume 57, No. 7. Reprinted here with corrected text

Effects of host sex and pregnancy on Trichinella Zimbabwensis infection in Sprague-Dawley rats and Balb C mice.

M. Sc. University of KwaZulu-Natal, Durban 2014.Trichinellosis is a zoonotic parasitic disease caused by nematode parasites of the genus Trichinella. Trichinella species infect a wide range of hosts including humans, domestic and wild animals. The main mode of human infection is through ingestion of raw or undercooked pork. The successful establishment and development of Trichinella parasite in a host is affected by various factors which include sex of host, environmental, immunological and hormonal. The objective of this study was to determine the effect of host sex and pregnancy on the establishment and development of Trichinella zimbabwensis in Sprague-Dawley rats and Balb C mice respectively. Rodents are the common reservoirs of Trichinella spp. in the domestic and sylvatic cycles and it was logical to determine the establishment and development of Trichinella zimbabwensis in Sprague-Dawley rats. The study on the effects of pregnancy and levels of progesterone and cortisol was done in Balb C mice and this was influenced by availability of mice in large quantities to conduct the experiments. Rats and mice are not widely different in their physiology and have been used interchangeably as host in previous Trichinella studies. Therefore it was important to use these animals as models for the study. In order to determine the effect of host sex on the establishment and development of T. zimbabwensis, 50 Sprague-Dawley rats were divided into two groups (25 males and 25 females) and orally infected with 7 Trichinella zimbabwensis muscle larvae per gram (LPG) of animal live weight. On days 5, 10, 15, 20 and 25 post-infection (PI), five animals from each group were sacrificed and the numbers of adult parasites in the intestine as well as larvae in muscles were determined. To determine the effect of host pregnancy, 90 female Balb C mice were divided into 3 groups of 30 mice each. Group 1 animals were orally infected with 50 LPG on day 0 of trial; group 2 animals were mated on day 0, but were not infected; group 3 animals were mated on day 0 and infected with 50 LPG on day 7 post-mating. On days 0, 7, 14, 21 and 28 PI for groups 1; days 0, 7, 14, 21 and 28 post-mating for group 2; and days 7, 14, 21, 28 and 35 post-mating for group 3, six animals from each group were sacrificed and the numbers of adult parasites in the intestines as well as larvae in the muscles were determined in infected groups. In addition, levels of the hormones progesterone and cortisol were measured in all groups at the same intervals. Results from the study showed a significantly higher number of Trichinella adults and larvae (P < 0.05) in male than in female Sprague-Dawley rats (four times higher adult worms and two times higher in muscle larvae in males than in females). On the other hand, pregnancy reduced the number of larvae establishing in muscles with progesterone levels significantly higher in pregnant than in non-pregnant Balb C mice (P < 0.05). This was attributed to the parasiticidal effect of progesterone against new-born larvae (NBL). This finding can be exploited when designing strategies to control and to treat the infection in rodents and humans. There were no significant differences in cortisol levels between pregnant and non-pregnant mice