Complement component C3 is required for protective innate and adaptive immunity to larval strongyloides stercoralis in mice.
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.
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Laura A
LA
Kerepesi
Jessica A
JA
Hess
Thomas J
TJ
Nolan
Gerhard A
GA
Schad
David
D
Abraham
D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate / Q000276:immunology*; D007814:Larva / Q000254:growth & development / Q000276:immunology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011951:Receptors, Complement / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017171:Strongyloides stercoralis / Q000254:growth & development / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology*
D003176:Complement C3; D003182:Complement C5; D016207:Cytokines; D008565:Membrane Proteins; D011951:Receptors, Complement; C085567:complement C3a receptor