The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis

Paul R. Giacomin, David L. Gordon, Marina Botto, Mohamed R. Daha, Sam Sanderson, Stephen M. Taylor, Lindsay A. Dent

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Complement may be important for immunity to infection with parasitic helminths, by promoting the recruitment of leukocytes to infected tissues and by modulating the function of cytotoxic effector leukocytes. However, the importance of complement in vivo during helminth infection is poorly understood. In this study, mice lacking classical (C1q-deficient), alternative (factor B-deficient) or all pathways of complement activation (C3-deficient) were used to assess the role of complement in immunity to the nematode Nippostrongylus brasiliensis. Double-mutant complement-deficient/IL-5 transgenic (Tg) mice were used to determine if complement is required for the strong eosinophil-dependent resistance to this parasite. Complement activation on larvae (C3 deposition), extracellular eosinophil peroxidase activity, larval aggregation and eosinophil recruitment to the skin 30 min post-injection (p.i.) of larvae were reduced in factor B-deficient mice. Inhibition of the C5a receptor with the antagonist PMX53 impaired eosinophil and neutrophil recruitment to the skin. C3 deposition on larvae was minimal by 150 min p.i. and at this time cell adherence, larval aggregation, eosinophil recruitment and degranulation were complement-independent. Factor B and C3 deficiency were associated with higher lung larval burdens in primary infections. Complement-deficient/IL-5 Tg mice were highly resistant to N. brasiliensis, suggesting that eosinophils can limit infection in a complement-independent manner. Potent secondary immunity was similarly complement-independent. In conclusion, although the alternative pathway is important for parasite recognition and leukocyte recruitment early in N. brasiliensis infections, the parasite soon becomes resistant to complement and other factors can compensate to promote eosinophil-dependent immunity.

Original languageEnglish (US)
Pages (from-to)446-455
Number of pages10
JournalMolecular Immunology
Volume45
Issue number2
DOIs
StatePublished - Jan 1 2008

Fingerprint

Nippostrongylus
Eosinophils
Immunity
Complement Factor B
Larva
Parasitic Diseases
Leukocytes
Complement Activation
Helminths
Interleukin-5
Transgenic Mice
Parasites
Infection
Anaphylatoxin C5a Receptor
Eosinophil Peroxidase
Skin
Complement C3
Injections
Neutrophil Infiltration
Lung

Keywords

  • Alternative pathway
  • Complement
  • Eosinophil
  • Helminth
  • Nippostrongylus brasiliensis

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Giacomin, P. R., Gordon, D. L., Botto, M., Daha, M. R., Sanderson, S., Taylor, S. M., & Dent, L. A. (2008). The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis. Molecular Immunology, 45(2), 446-455. https://doi.org/10.1016/j.molimm.2007.05.029

The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis. / Giacomin, Paul R.; Gordon, David L.; Botto, Marina; Daha, Mohamed R.; Sanderson, Sam; Taylor, Stephen M.; Dent, Lindsay A.

In: Molecular Immunology, Vol. 45, No. 2, 01.01.2008, p. 446-455.

Research output: Contribution to journalArticle

Giacomin, Paul R. ; Gordon, David L. ; Botto, Marina ; Daha, Mohamed R. ; Sanderson, Sam ; Taylor, Stephen M. ; Dent, Lindsay A. / The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode Nippostrongylus brasiliensis. In: Molecular Immunology. 2008 ; Vol. 45, No. 2. pp. 446-455.
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