Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in mice

Abstract

SummaryStrongyloides stercoralis is an intestinal nematode capable of chronic, persistent infection and hyperinfection of the host; this can lead to dissemination, mainly in immunosuppressive states, in which the infection can become severe and result in the death of the host. In this study, we investigated the immune response against Strongyloides venezuelensis infection in major histocompatibility complex (MHC) class I or class II deficient mice. We found that MHC II )/) animals were more susceptible to S. venezuelensis infection as a result of the presence of an elevated number of eggs in the faeces and a delay in the elimination of adult worms compared with wild-type (WT) and MHC I )/) mice. Histopathological analysis revealed that MHC II )/) mice had a mild inflammatory infiltration in the small intestine with a reduction in tissue eosinophilia. These mice also presented a significantly lower frequency of eosinophils and mononuclear cells in the blood, together with reduced T helper type 2 (Th2) cytokines in small intestine homogenates and sera compared with WT and MHC I )/) animals. Additionally, levels of parasite-specific immunoglobulin M (IgM), IgA, IgE, total IgG and IgG1 were also significantly reduced in the sera of MHC II )/) infected mice, while a non-significant increase in the level of IgG2a was found in comparison to WT or MHC I )/) infected mice. Together, these data demonstrate that expression of MHC class II but not class I molecules is required to induce a predominantly Th2 response and to achieve efficient control of S. venezuelensis infection in mice.

Differences in the Importance of Mast Cells, Basophils, IgE, and IgG versus That of CD4+T Cells and ILC2 Cells in Primary and Secondary Immunity to Strongyloides venezuelensis

“…We found that T and B cell-deficient Rag2 -/-mice exhibited a 20-day delay (i.e., requiring 32 days in total) in cessation of S. venezuelensis egg excretion during primary infections and a 25-day delay (i.e., requiring 37 days in total) in the secondary infection (versus no eggs detected during secondary infections in any of the wild-type mice) (Fig. 3A), underscoring the importance of an adaptive immune response for effective secondary immune responses to this nematode (8,11,13,14,41,(46)(47)(48). In addition, we confirmed that the number of adult worms in the intestines on day 8 of the primary infection was significantly higher in the Rag2 -/-mice than in the corresponding wild-type mice (Fig.…”

Increased susceptibility to Strongyloides venezuelensis infection is related to the parasite load and absence of major histocompatibility complex (MHC) class II molecules

“…The entire length of the small intestine, (the four pieces as described above) was examined histologically and the inflammatory infiltrate was graded according to leukocyte infiltration in the lamina propria (LP), epithelium and submucosa as previously described (Rodrigues et al, 2009). The inflammatory score was represented by arbitrary units: 0-2, mild; 2-4, moderate; 4-6, severe; above 6, very severe, as previously described (Rodrigues et al, 2009). …”

“…Previous studies from our group demonstrated that intestinal establishment of S. venezuelensis is affected by the absence of major histocompatibility complex (MHC) class II molecules during parasite infection. The MHC class II deficient mice (MHC II À/À ) presented higher susceptibility to S. venezuelensis infection, with impaired responses to the worm, suggesting that the failure of MHC class II expression affects the antigen presentation to CD4 + T cells that is necessary for the initiation of an effective Th2 response against the parasite (Abe and Nawa, 1988;Goncalves et al, 2008;Rodrigues et al, 2009).…”

“…In human and murine models the infection is characterized by systemic eosinofilia (Korenaga et al, 1991;Nawa et al, 1994;Onah and Nawa, 2000), production of cytokines such as IL-3, IL-4, IL-5 and IL-13 with subsequent secretion of specific IgM, IgG, IgG1, IgA and IgE, essential to the elimination of the parasite (Abe and Nawa, 1988;Onah and Nawa, 2000;Schilter et al, 2010;Goncalves et al, 2012a). S. venezuelensis naturally infects rats and has been used in experimental models (Machado et al, 2005;Negrão-Correa et al, 2006) aimed to study the immunoprotection and immunoregulation aspects of the disease since it evokes similar innate and acquired immune response in mice as does S. stercoralis in humans (Rodrigues et al, 2009). Previous studies from our group demonstrated that intestinal establishment of S. venezuelensis is affected by the absence of major histocompatibility complex (MHC) class II molecules during parasite infection.…”

Roles of Major Histocompatibility Complex Class II in Inducing Protective Immune Responses to Influenza Vaccination

“…MHC-II molecules were required for the development, maturation, and function of CD4 ϩ T cells (13). Previous studies demonstrated that MHC-II KO mice were not effective in controlling infection with the parasites Schistosoma mansoni (16), Leishmania major (42), Mycobacterium bovis bacilli Calmette-Guerin (18), Strongyloides venezuelensis (43), and Theiler's virus (20). Meanwhile, other studies reported few or no obvious defects on virus clearance of Sendai virus or influenza virus in mice lacking the MHC-II molecule, after sublethal infection, indicating that virus-specific CD8 ϩ cytotoxic T lymphocyte precursors are intact in MHC-II KO mice (14,19).…”