Publikationsdatenbank

Cellular analysis of susceptibility and resistance to a roundworm infection in the mouse model (2025)

Art

Hochschulschrift

Autor

Elizalde Velázquez, Luis Enrique (WE 6)

Quelle

Berlin, 2025 — 92 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/49847

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51834
immunologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Helminths contribute a large proportion of the global burden of disease. Mainly by causing gastrointestinal infections of varying intensity in humans and animals. We asked whether commensal bacteria in the host gut can modulate the immune response against the gastrointestinal helminths, whether depletion of the microbiota with antibiotics would affect anthelmintic type 2 immune responses in the rodent model of hookworm infections. Our results showed that antibiotic treatment resulted in microbiota depletion, but neither worm burden nor female egg production was affected. Upon secondary infection with H. polygyrus, worm burdens increased in antibiotic-treated mice, suggesting that a lack of microbiota had created a supportive environment for the worms to establish themselves. Immune responses were not affected by microbiota depletion. Similar type 2 cytokines and Th2 cell frequencies were found during primary infection, during the memory phase, and after challenge infection. Interestingly, tissue-resident memory cells expressing CD69 found in the peritoneal cavity were significantly enriched during secondary infection, suggesting that the peritoneum is a strong reservoir for memory cells. Antibody responses similar to cellular responses did not change in the presence or absence of microbiota. The only increase in antibody isotype IgE was associated with the memory phase of the response, suggesting a possible enhancement of IgE responses due to the lack of bacteria coupled with the accumulation of allergens from the worm. The host and worm metabolic changes analyzed using NADPH fluorescence lifespan imaging also showed no significant changes in the presence or absence of microbiota. Overall, type 2 immune responses against a gastrointestinal nematode as well as metabolic changes of hosts and nematodes are robust and no effect of the presence or absence of microbiota was shown by prolonged antibiotic treatment. On the other hand, this work investigated the different intensity of infection of gastrointestinal helminths in natural hosts by analyzing the hepato-tracheal migration of Ascaris suum in two different mouse strains. A susceptible C57BL/6 mouse and a resistant CBA mouse. We asked whether the tendency of individuals to be more or less susceptible is related to different innate immune responses elicited during tissue migration. Interestingly, contrary to our expectations, we found that the susceptible strain had high levels of inflammation, while the resistant strain had no inflammation at all. The inflammation caused by the susceptible strain was associated with the expression of type 2 cytokines, namely IL-5 and IL-13, by innate lymphoid cells, which subsequently responded to the recruitment of eosinophils and alternative (M2) macrophages to the mice lungs followed. Eosinophil-depleted mice were subsequently examined. The results showed that the presence of eosinophils was not related to protection, as reflected in similar larval burdens between eosinophil-deficient and eosinophil-sufficient mice. Because we detected high levels of eosinophil peroxidase in the serum of susceptible mice at the lung stage of infection, these cells may be more affected by the pathology. In conclusion, these works showed that a strong type 2 immune response is associated with susceptibility, while the resistance associated with CBA mice requires further investigation since no immunological parameter analyzed indicates an increased susceptibility to the infection.