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Skin mast cells control T cell‐dependent host defense in Leishmania major infections
Author(s) -
Maurer Marcus,
Lopez Kostka Susanna,
Siebenhaar Frank,
Moelle Katharina,
Metz Martin,
Knop Jürgen,
Stebut Esther
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-5860com
Subject(s) - leishmania major , immunology , biology , cutaneous leishmaniasis , proinflammatory cytokine , immunity , inflammation , innate immune system , mast cell , immune system , cytokine , intracellular parasite , priming (agriculture) , leishmania , leishmaniasis , parasite hosting , botany , germination , world wide web , computer science
Mast cells (MCs) initiate protective im‐ munity against bacteria. Here we demonstrate that MCs also contribute to the control of parasitic skin infections by Leishmania major. L. major ‐infected MC‐defi‐cient Kit W /Kit W‐v mice developed markedly larger skin lesions than did normal Kit +/+ mice (>2‐fold), and cutaneous reconstitution with MCs resulted in normalization of lesion development. Kit W /Kit W‐v lesions contained significantly more parasites, and infections resulted in enhanced spreading of parasites to the spleens as compared to controls. In addition, recruitment of proinflammatory neutrophils, macrophages, and dendritic cells (DCs) in infected mice was MC dependent. In the absence of MCs, reduced numbers of lesional DCs were associated with decreased production of Th1‐promoting interleukin (IL)‐12. Antigen‐specific T cell priming was delayed in Kit W /Kit W‐v mice and cytokine responses were skewed towards Th2. Notably, local skin MC reconstitution at sites of infection was sufficient for the induction of systemic protection. Thus, MC‐mediated control of L. major infections is not limited to the induction of local inflammation. Instead, MCs contribute significantly to local DC recruitment, which mediates protective immunity. These findings extend the view of MCs as salient sentinels of innate immunity to complex host defense reactions against intracellular pathogens.—Maurer, M., Lopez Kostka, S., Siebenhaar, F., Moelle, K., Metz, M., Knop, J., von Stebut, E. Skin mast cells control T cell‐dependent host defense in Leishmania major infections. FASEB J. 20, 2460–2467 (2006)