title: PIR-B-deficient mice are susceptible to Salmonella infection.
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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Torii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oka
authors.forename: Muneki
authors.initials: M
authors.lastname: Hotomi
authors.forename: William H
authors.initials: WH
authors.lastname: Benjamin
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: John F
authors.initials: JF
authors.lastname: Kearney
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kubagawa