BLT1 mediates commensal bacteria-dependent innate immune signals to enhance antigen-specific intestinal IgA responses

Mucosal Immunol. 2019 Sep;12(5):1082-1091. doi: 10.1038/s41385-019-0175-z. Epub 2019 May 29.

Abstract

Leukotriene B4 receptor 1 (BLT1) triggers the migration of granulocytes and activated T cells; however, its role in B-cell function remains unclear. Here we report that BLT1 is required to induce the production of antigen-specific IgA against oral vaccine through mediating innate immune signals from commensal bacteria. B cells acquire BLT1 expression during their differentiation to IgA+ B cells and plasma cells in Peyer's patches and the small intestinal lamina propria, respectively. BLT1 KO mice exhibited impaired production of antigen-specific fecal IgA to oral vaccine despite normal IgG responses to systemically immunized antigen. Expression of MyD88 was decreased in BLT1 KO gut B cells and consequently led to diminished proliferation of commensal bacteria-dependent plasma cells. These results indicate that BLT1 enhances the proliferation of commensal bacteria-dependent IgA+ plasma cells through the induction of MyD88 and thereby plays a key role in the production of antigen-specific intestinal IgA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Epitopes / immunology*
  • Gastrointestinal Microbiome / immunology*
  • Immunity, Innate*
  • Immunization
  • Immunoglobulin A, Secretory / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Male
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / metabolism
  • Peyer's Patches / immunology
  • Peyer's Patches / metabolism
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Receptors, Leukotriene B4 / genetics*
  • Receptors, Leukotriene B4 / metabolism
  • Signal Transduction
  • Vaccines / administration & dosage
  • Vaccines / immunology

Substances

  • Epitopes
  • Immunoglobulin A, Secretory
  • Ltb4r1 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Leukotriene B4
  • Vaccines