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

Abstract

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.

Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to LarvalStrongyloides stercoralisin Mice

“…In vitro studies have demonstrated that the serum components complement and fibronectin are required for eosinophil binding and degranulation resulting in the killing of N. brasiliensis larvae (58). Complement component C3 has been shown to be required for innate immunity to S. stercoralis (35). It has also been reported that the purified human eosinophil granule products major basic protein and eosinophil cationic protein are directly toxic to larval S. stercoralis in the absence of any other cells or factors (51).…”

Scabies Mite Inactivated Serine Protease Paralogs Inhibit the Human Complement System

“…In addition, a surface FcR might bind Ig in an unfavorable orientation and thereby limit its ability to activate complement. In mice infested with larval Strongyloides stercoralis, C3 was not required for the development of adaptive immunity, but was necessary for the larval killing process during both protective innate and adaptive immune responses (13).…”

Human and Mouse Macrophages Collaborate with Neutrophils To Kill Larval Strongyloides stercoralis

“…In mice, several components of protective primary and secondary immunity to the parasite have been described (17). Molecules from larval S. stercoralis directly recruit granulocytes to the parasite microenvironment (18)(19)(20), where they kill the parasite in collaboration with complement component C3 (21), eosinophil major basic protein, and neutrophil-derived myeloperoxidase (22,23). The cellular composition of the parasite microenvironment in naive mice consists of high numbers of neutrophils, eosinophils, and macrophages (22).…”