Pathogenic role of B cells and antibodies in murine Leishmania amazonensis infection

Nanchaya Wanasen, Lijun Xin, Lynn Soong

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Leishmania amazonensis infection, occurring predominantly in Central and South America, can manifest itself in several forms, including those of cutaneous and diffuse cutaneous leishmaniasis. The outcome of L. amazonensis infection depends largely on host immune responses to the parasites. While CD4+ T cell activation is a prerequisite for pathogenesis in L. amazonensis-infected mice, the roles of B cells and their antibody production are unclear. In this study, we provide evidence suggesting that B cells and antibodies are involved in disease pathogenesis. We documented a correlation between B cell activation and lesion progress in immunocompetent mice. In the absence of functional B cells and antibodies, JhD mice showed a delayed onset of disease and developed small lesions. Histological examination of these mice revealed a significant reduction in CD4+ and CD8+ T cells, but not in MAC1+ macrophages, at the infection site. In contrast to the wild-type mice that showed typical tissue necrosis, L. amazonensis-infected JhD mice showed no or minimal signs of necrotic foci. A marked reduction in CD4+ T cell proliferation and cytokine (IFN-γ and IL-10) production in infected JhD mice suggested an involvement of B cells and antibodies in the priming of parasite-specific T cells. This notion was further supported by the observations that adoptive transfer of B cells or antibodies could restore CD4+ T cell activation and migration in infected JhD mice. Moreover, antibody coating of parasites could stimulate dendritic cells to produce high levels of cytokines and increase their ability to prime nai{dotless}̈ve CD4+ T cells. Since CD4+ T cells are crucial to disease pathogenesis, this study suggests that B cells and their antibody production enhanced L. amazonensis infection, partially by promoting T cell priming and cellular migration to the infection site.

Original languageEnglish (US)
Pages (from-to)417-429
Number of pages13
JournalInternational Journal for Parasitology
Volume38
Issue number3-4
DOIs
StatePublished - Mar 2008

Keywords

  • Antibodies
  • B cells
  • Cellular recruitment
  • Cutaneous leishmaniasis
  • Protozoan parasites
  • T cell activation

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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