Role of IL-5 in Innate and Adaptive Immunity to Larval<i>Strongyloides stercoralis</i>in Mice

Herbert, De’Broski R.; Lee, James J.; Lee, Nancy A.; Nolan, Thomas J.; Schad, Gerhard A.; Abraham, David

doi:10.4049/jimmunol.165.8.4544

Cited by 112 publications

(122 citation statements)

References 47 publications

(62 reference statements)

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“…Indeed, basophils are a major source of IL-4 during secondary immune responses, and were shown to promote secondary immunity against N. brasiliensis (26,(45)(46)(47). Thus, while multiple redundant mechanisms are functioning during secondary challenge infection, our data support a hypothesis that eosinophils serve a predominant role in worm destruction during anamnestic immunity against GI nematodes (48,49).…”

Section: Discussionsupporting

confidence: 73%

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

Hung

Lewkowich

Dawson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

187

174

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Parasitic helminths are a major cause of chronic human disease, affecting more than 3 billion people worldwide. Host protection against most parasitic helminths relies upon Type 2 cytokine production, but the mechanisms that regulate interleukin (IL) 4 and 13 production from CD4 + T helper 2 cells (T H 2) and innate lymphoid type 2 cells (ILC2s) remain incompletely understood. The epithelial cell-derived cytokines IL-25 and IL-33 promote Type 2 responses, but the extent of functional redundancy between these cytokines is unclear and whether Type 2 memory relies upon either IL-25 or IL-33 is unknown. Herein, we demonstrate a pivotal role for IL-33 in driving primary and anamnestic immunity against the rodent hookworm Nippostrongylus brasiliensis. IL-33-deficient mice have a selective defect in ILC2-derived IL-13 during both primary and secondary challenge infections but generate stronger canonical CD4 + T helper 2 cells responses (IL-4, IgE, mast cells, and basophils) than WT controls. Lack of IL-13 production in IL-33-deficient mice impairs resistin-like molecule beta (RELMβ) expression and eosinophil recruitment, which are two mechanisms that eliminate N. brasiliensis parasites from infected hosts. Thus, IL-33 is requisite for IL-13 but not IL-4-driven Type 2 responses during hookworm infection. mucosal immunity | gastrointestinal nematode | inflammation

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Section: Discussionsupporting

confidence: 73%

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

Hung

Lewkowich

Dawson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

187

174

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“…In addition, mice deficient in circulating IgM (secIgM Ϫ/Ϫ ) have abrogated clearance of primary and secondary L3 infections (25). IgM is also needed in mice for protection against secondary infection of the nematode Strongyloides stercoralis (26). Overall, therefore, the lower levels of parasitespecific IgM found in B. malayi Mf-infected MBL-A Ϫ/Ϫ mice could account for the enhanced Mf survival.…”

Section: Discussionmentioning

confidence: 95%

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Carter

Sumiya

Reilly

et al. 2007

The Journal of Immunology

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To investigate the role of mannose-binding lectin-A (MBL-A) in protection against infectious disease, MBL-A−/−-deficient mice were generated. Using a well-characterized mouse model of human filarial nematode infection, nematode survival and protective immune responses were tested in vivo. Blood-borne Brugia malayi microfilariae survived for significantly longer time periods in MBL-A−/− than in wild-type (WT) mice. However, no differences in either splenic cytokine responses or induction of leukocytes in the blood were observed. A profound abrogation of Ag-specific IgM levels was measured in B. malayi-infected MBL-A−/− mice, and some IgG isotypes were higher than those observed in WT animals. To establish whether there was a defect in Ab responses per se in MBL-A−/− mice or the effect was specific to filarial infection, we immunized these mice with OVA or a carbohydrate-free protein. Significantly, Ag-specific IgM responses were defective to both of these Ags, and Ag-specific IgG responses were largely unaffected. Furthermore, in naive mice, total IgM levels did not differ between MBL-A−/− and WT mice. This article describes the first demonstration that MBL-A may function independently of MBL-C and suggests that MBL-A, like other C-type lectins and members of the complement cascade, is intimately involved in the priming of the humoral Ab response.

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“…C3b appears to be the active component of C3 and possibly cooperates with eosinophils, facilitating eosinophil degranulation and larval death during the innate immune response (18,45). C3b also appears to be the active component of C3 during the adaptive response, and it functions at the terminal end of the killing process.…”

Section: Discussionmentioning

confidence: 99%

“…C3b also appears to be the active component of C3 during the adaptive response, and it functions at the terminal end of the killing process. Killing of larval S. stercoralis by immunized mice is dependent on the interaction among IgM (19,20), neutrophils (18,20), and C3. It is hypothesized that the presence of IgM, generated during the adaptive immune response, increases the amount of fixed C3b present on the surface of the larvae, thereby increasing the efficiency by which neutrophils eliminate larval S. stercoralis.…”

Section: Discussionmentioning

confidence: 99%

“…In mice, the immune mechanisms capable of killing larval S. stercoralis have been studied on a variety of mouse backgrounds, including C57BL/6J, BALB/cJ, BALB/cByJ, and CBA/J (15)(16)(17). Innate protective immunity, evaluated 3 days after infection of naive mice, was shown to be IL-5 and eosinophil dependent (18). Adaptive protective immunity developed after immunization of mice with live larvae and resulted in ϳ90% of challenge larvae killed within 1 day postchallenge (15).…”

mentioning

confidence: 99%

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Complement Component C3 Is Required for Protective Innate and Adaptive Immunity to Larval Strongyloides stercoralis in Mice

Kerepesi

Hess

Nolan

et al. 2006

The Journal of Immunology

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This study examines the role of complement components C3 and C5 in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. Larval survival in naive C3−/− mice was increased as compared with survival in wild-type mice, whereas C3aR−/− and wild-type mice had equivalent levels of larval killing. Larval killing in naive mice was shown to be a coordinated effort between effector cells and C3. There was no difference between survival in wild-type and naive C5−/− mice, indicating that C5 was not required during the innate immune response. Naive B cell-deficient and wild-type mice killed larvae at comparable levels, suggesting that activation of the classical complement pathway was not required for innate immunity. Adaptive immunity was equivalent in wild-type and C5−/− mice; thus, C5 was also not required during the adaptive immune response. Larval killing was completely ablated in immunized C3−/− mice, even though the protective parasite-specific IgM response developed and effector cells were recruited. Protective immunity was restored to immunized C3−/− mice by transferring untreated naive serum, but not C3-depleted heat-inactivated serum to the location of the parasites. Finally, immunized C3aR−/− mice killed larvae during the adaptive immune response as efficiently as wild-type mice. Therefore, C3 was not required for the development of adaptive immunity, but was required for the larval killing process during both protective innate and adaptive immune responses in mice against larval S. stercoralis.

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Role of IL-5 in Innate and Adaptive Immunity to LarvalStrongyloides stercoralisin Mice

Cited by 112 publications

References 47 publications

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms

Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection

Complement Component C3 Is Required for Protective Innate and Adaptive Immunity to Larval Strongyloides stercoralis in Mice

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