PIR-B-deficient mice are susceptible to Salmonella infection.

Academic Article

Abstract

  • Paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) isoforms are expressed by many hematopoietic cells, including B lymphocytes and myeloid cells. To determine the functional roles of PIR-A and PIR-B in primary bacterial infection, PIR-B-deficient (PIR-B(-/-)) and wild-type (WT) control mice were injected i.v. with an attenuated strain of Salmonella enterica Typhimurium (WB335). PIR-B(-/-) mice were found to be more susceptible to Salmonella infection than WT mice, as evidenced by high mortality rate, high bacterial loads in the liver and spleen, and a failure to clear bacteria from the circulation. Although blood levels of major cytokines and Salmonella-specific Abs were mostly comparable in the two groups of mice, distinct patterns of inflammatory lesions were found in their livers at 7-14 days postinfection: diffuse spreading along the sinusoids in PIR-B(-/-) mice vs nodular restricted localization in WT mice. PIR-B(-/-) mice have more inflammatory cells in the liver but fewer B cells and CD8(+) T cells in the spleen than WT mice at 14 days postinfection. PIR-B(-/-) bone marrow-derived macrophages (BMMphi) failed to control intracellular replication of Salmonella in vitro, in part due to inefficient phagosomal oxidant production, when compared with WT BMMphi. PIR-B(-/-) BMMphi also produced more nitrite and TNF-alpha upon exposure to Salmonella than WT BMMphi did. These findings suggest that the disruption of PIR-A and PIR-B balance affects their regulatory roles in host defense to bacterial infection.
  • Published In

    Keywords

  • Animals, Antibodies, Bacterial, Cytokines, Female, Genetic Predisposition to Disease, Inflammation Mediators, Liver, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Isoforms, Receptors, Immunologic, Salmonella Infections, Animal, Salmonella typhimurium, Spleen
  • Pubmed Id

  • 6318728
  • Author List

  • Torii I; Oka S; Hotomi M; Benjamin WH; Takai T; Kearney JF; Briles DE; Kubagawa H
  • Start Page

  • 4229
  • End Page

  • 4239
  • Volume

  • 181
  • Issue

  • 6