Paired Immunoglobulin-like receptors of activating (PIR-A) and inhibitory (PIR-B) isoforms are expressed by many blood cell types including B cells, dendritic cells, monocyte/macrophages, granulocytes, mast cells and megakaryocyte/platelets. To determine the role of PIR-B in bacterial infection, PIR-B deficient (PIR-B−/−) and control C57BL/6 mice of the same age and sex were infected intravenously with the attenuated strain of Salmonella typhimurium (WB335). When injected with high doses of bacteria (5 × 104 ∼ 5 × 106 CFU), both types of mice died within 3 to 14 days post infection. When given small doses (103 ∼ 104 CFU), however, PIR-B−/− mice exhibited progressively increasing morbidity beginning at 4-day post-infection over a 4-week period, whereas many control mice could survive (see Figure). PIR-B−/− mice were found to have higher bacterial loads in liver, spleen and lungs than the control mice and bacteremia at days 3 and 7 post-infection. In liver histology typhoid nodules were observed as early as day 1 and their incidence increased during the next six days in both groups of mice. However, quite distinct changes were observed at day 7: in control mice inflammatory cellular lesions were localized and exhibited nodular distribution, whereas in PIR-B−/− mice mononuclear cells infiltrated along the liver sinusoids and exhibited a spreading distribution. There were no significant differences in plasma levels of liver enzymes (ATL, AST and ALK), cytokines (TNFα, IL-10 and IFNγ) and antibodies (IgM, IgG and IgA) against Salmonella between PIR-B−/− and control mice. While splenic lymphoid and myeloid subsets were indistinguishable during the first week of infection, the increases of CD19+ B and CD8+ T cells in infected PIR-B−/− mice were not as marked as those in infected control mice at day 14 post-infection (see Table). For phagocytic cell functions ex vivo, there were no differences in phagocytosis and intracellular killing of bacteria and superoxide anion release between PIR-B−/− and control mice. However, PIR-B−/− macrophages were found to release more nitrite and TNFα upon bacteria stimulation than the control macrophages. These results suggest that PIR-B plays an important regulatory role in bacterial infection.

(Supported by NIH/NIAID grants AI42127 and AI52243).

Mac-1+ MΦCD4 + TCD8+ TCD19+ B
cell numbers (× 107), mean ± 1 S.D. 
Uninfected Control 1.3 ± 0.6 * 1.4 ± 0.4 0.7 ± 0.3 5.1 ± 1.8 
Uninfected PIR-B−/− 1.2 ± 0.3 1.5 ± 0.2 1.2 ± 0.2 4.9 ± 0.3 
Infected Control 19.4 ± 7.0 5.5 ± 1.5 2.6 ± 0.7 10.0 ± 2.6 
Infected PIR-B−/− 16.5 ± 2.3 4.2 ± 2.1 1.3 ± 0.6 4.5 ± 1.3 
Mac-1+ MΦCD4 + TCD8+ TCD19+ B
cell numbers (× 107), mean ± 1 S.D. 
Uninfected Control 1.3 ± 0.6 * 1.4 ± 0.4 0.7 ± 0.3 5.1 ± 1.8 
Uninfected PIR-B−/− 1.2 ± 0.3 1.5 ± 0.2 1.2 ± 0.2 4.9 ± 0.3 
Infected Control 19.4 ± 7.0 5.5 ± 1.5 2.6 ± 0.7 10.0 ± 2.6 
Infected PIR-B−/− 16.5 ± 2.3 4.2 ± 2.1 1.3 ± 0.6 4.5 ± 1.3 
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Figure

Topics:
antibodies, bacteremia, bacterial infections, cd19 antigens, cytokine, enteric fever, immunoglobulin a, immunoglobulin g, immunoglobulin m, immunoglobulins

Author notes

Disclosure: No relevant conflicts of interest to declare.

2007, The American Society of Hematology
2007
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