Acquired immunity to Trichuris muris in the albino laboratory mouse

362

332

IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4+ Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.

Section: Discussionmentioning

confidence: 99%

IL-33, a Potent Inducer of Adaptive Immunity to Intestinal Nematodes

Humphreys

Hepworth

et al. 2008

362

332

“…Following sterile cure of a primary infection with Trichuris, mice exhibit enhanced resistance to reinfection (7,27). Although CD4 ϩ T cells are critical for primary worm expulsion (28), it is not known whether memory CD4 ϩ T cells develop during primary infection nor whether these cells are required for resistance to reinfection.…”

Section: Long-term Trichuris-specific Cd4 ϩ Th2 Memory In the Absencementioning

confidence: 99%

“…For instance, re-exposure to the GI nematode Trichuris muris leads to rapid immune-mediated expulsion of a secondary infection (7). In common with other GI helminths, immunity to a primary infection with Trichuris is dependent upon CD4 ϩ Th type 2 (Th2) cells that develop in the GALT, produce IL-4 and IL-13, and mediate physiological changes in the GI tract (including alterations in epithelial cell turnover, goblet cell hyperplasia, and expression of resistin-like molecule (RELM)␤) associated with clearance of the worms and sterile immunity (8 -12).…”

mentioning

confidence: 99%

Persistence and Function of Central and Effector Memory CD4+ T Cells following Infection with a Gastrointestinal Helminth

Zaph

Rook

Goldschmidt

et al. 2006

Immunity in the gastrointestinal tract is important for resistance to many pathogens, but the memory T cells that mediate such immunity are poorly characterized. In this study, we show that following sterile cure of a primary infection with the gastrointestinal parasite Trichuris muris, memory CD4+ T cells persist in the draining mesenteric lymph node and protect mice against reinfection. The memory CD4+ T cells that developed were a heterogeneous population, consisting of both CD62Lhigh central memory T cells (TCM) and CD62Llow effector memory T cells (TEM) that were competent to produce the Th type 2 effector cytokine, IL-4. Unlike memory T cells that develop following exposure to several other pathogens, both CD4+ TCM and TEM populations persisted in the absence of chronic infection, and, critically, both populations were able to transfer protective immunity to naive recipients. CD62LhighCD4+ TCM were not apparent early after infection, but emerged following clearance of primary infection, suggesting that they may be derived from CD4+ TEM. Consistent with this theory, transfer of CD62LlowCD4+ TEM into naive recipients resulted in the development of a population of protective CD62LhighCD4+ TCM. Taken together, these studies show that distinct subsets of memory CD4+ T cells develop after infection with Trichuris, persist in the GALT, and mediate protective immunity to rechallenge.

“…Given that T. muris forms syncitial tunnels within the epithelium of the cecum and proximal colon (24), IEL are especially close to the parasites and their Ag. Therefore, IEL may play a major role in the immune response to and, ultimately, the elimination of T. muris.…”

mentioning

confidence: 99%

The Characterization of Intraepithelial Lymphocytes, Lamina Propria Leukocytes, and Isolated Lymphoid Follicles in the Large Intestine of Mice Infected with the Intestinal Nematode Parasite Trichuris muris

Little

Bell

Cliffe

et al. 2005

Despite a growing understanding of the role of cytokines in immunity to the parasitic helminth Trichuris muris, the local effector mechanism culminating in the expulsion of worms from the large intestine is not known. We used flow cytometry and immunohistochemistry to characterize the phenotype of large intestinal intraepithelial lymphocytes (IEL) and lamina propria leukocytes (LPL) from resistant and susceptible strains of mouse infected with T. muris. Leukocytes accumulated in the epithelium and lamina propria after infection, revealing marked differences between the different strains of mouse. In resistant mice, which mount a Th2 response, the number of infiltrating CD4+, CD8+, B220+, and F4/80+ IEL and LPL was generally highest around the time of worm expulsion from the gut, at which point the inflammation was dominated by CD4+ IEL and F4/80+ LPL. In contrast, in susceptible mice, which mount a Th1 response, the number of IEL and LPL increased more gradually and was highest after a chronic infection had developed. At this point, CD8+ IEL and F4/80+ LPL were predominant. Therefore, this study reveals the local immune responses underlying the expulsion of worms or the persistence of a chronic infection in resistant and susceptible strains of mouse, respectively. In addition, for the first time, we illustrate isolated lymphoid follicles in the large intestine, consisting of B cells interspersed with CD4+ T cells and having a central zone of rapidly proliferating cells. Furthermore, we demonstrate the organogenesis of these structures in response to T. muris infection.