Naïve B cells reduce fungal dissemination in cryptococcus neoformans infected Rag1-/- mice

Chad Dufaud, Johanna Rivera, Soma Rohatgi, Liise Anne Pirofski

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

IgM and B-1 cell deficient mice exhibit early C. neoformans dissemination from lungs to brain, but a definitive role for B cells in conferring resistance to C. neoformans dissemination has not been established. To address this question, we developed an intranasal (i.n.) C. neoformans infection model in B and T cell deficient Rag1-/- mice and found they also exhibit earlier fungal dissemination and higher brain CFU than wild-type C57Bl/6 (wild-type) mice. To probe the effect of B cells on fungal dissemination, Rag1-/- mice were given splenic (intravenously) or peritoneal (intraperitoneally) B cells from wild-type mice and infected i.n. with C. neoformans 7 d later. Mice that received B cells had lung histopathology resembling wild type mice 14 d post-infection, and B-1, not B-2 or T cells in their lungs, and serum and lung IgM and IgG 21 d post-infection. Lung CFU were comparable in wild-type, Rag1-/-, and Rag1-/- mice that received B cells 21 d post-infection, but brain CFU were significantly lower in mice that received B cells than Rag1-/- mice that did not. To determine if natural antibody can promote immunity in our model, we measured alveolar macrophage phagocytosis of C. neoformans in Rag1-/- mice treated with naive wild-type IgM-sufficient or sIgM-/- IgM-deficient sera before infection. Compared to IgM-deficient sera, IgM-sufficient sera significantly increased phagocytosis. Our data establish B cells are able to reduce early C. neoformans dissemination in mice and suggest natural IgM may be a key mediator of early antifungal immunity in the lungs.

Original languageEnglish (US)
Pages (from-to)173-184
Number of pages12
JournalVirulence
Volume9
Issue number1
DOIs
StatePublished - Oct 3 2018

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Keywords

  • Adoptive transfer
  • B cell
  • B-1 B cell
  • Brain infection
  • Cryptococcus neoformans
  • Fungal dissemination
  • IgM
  • Lung infection
  • Rag1 mouse

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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