Influence of CR3 (CD11b/CD18) Expression on Phagocytosis of Bordetella pertussis by Human Neutrophils

Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA.
Infection and Immunity (Impact Factor: 3.73). 12/2005; 73(11):7317-23. DOI: 10.1128/IAI.73.11.7317-7323.2005
Source: PubMed


CR3 (CD11b/CD18) is expressed on neutrophils, and the engagement of CR3 can promote phagocytosis. CR3 serves as the receptor
for the Bordetella pertussis adhesin filamentous hemagglutinin (FHA) and for the adenylate cyclase toxin (ACT), which blocks neutrophil function. The
influence of CR3, FHA, and ACT on the phagocytosis of B. pertussis by human neutrophils was examined. The surface expression and function of CR3 are regulated. Tumor necrosis factor alpha
(TNF-α) and gamma interferon (IFN-γ) increased CR3 surface expression, but only TNF-α increased the ability of neutrophils
to phagocytose B. pertussis, suggesting that elevated CR3 expression alone is not sufficient to promote phagocytosis. Purified FHA and pertussis toxin
also increased the surface expression of CR3 on neutrophils, while ACT and the B subunit of pertussis toxin did not affect
CR3 expression. FHA-mediated attachment to CR3 can lead to phagocytosis, especially in the absence of ACT. FHA mutants failed
to attach and were not phagocytosed by neutrophils. Similarly, an antibody to CR3 blocked both attachment and phagocytosis.
The addition of exogenous FHA enhanced the attachment and phagocytosis of wild-type B. pertussis and FHA mutants. Mutants lacking the SphB1 protease, which cleaves FHA and allows the release of FHA from the bacterial surface,
were phagocytosed more efficiently than wild-type bacteria. ACT mutants were efficiently phagocytosed, but wild-type B. pertussis or ACT mutants plus exogenous ACT resisted phagocytosis. These studies suggest that the activation and surface expression
of CR3, FHA expression, and the efficiency of ACT internalization all influence whether B. pertussis will be phagocytosed and ultimately killed by neutrophils.

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    • "SphB1 is a serine protease which plays an essential role in the maturation of the adhesin and immune-modulating factor FHA [34]. Previous studies have shown that deletion of the sphB1 gene dramatically attenuated the ability of B. pertussis to infect mice [35] and enhanced phagocytosis [36]. Taken together with our observation that sphB1 is not expressed at high levels during infection, this gene represents a very attractive target because even low concentrations of neutralizing antibodies may be sufficient for protection. "
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    • "The cytokines induced by FHA might indirectly promote B. pertussis binding to host cells; IL-8, SCYA2/CCL2, GRO1/CXCL1, TNF-α, and IFN-γ, all induced at least at the transcriptional level by FHA (and in some cases, shown at the level of secreted protein), are known to promote expression of CD11b/CD18 (CR3) [49]–[51] which may serve as a receptor for FHA at the surface of neutrophils and monocytes [9], [52]. FHA might also influence host cell-cell interactions by up-regulating ICAM1 at the surface of PBMCs, similar to the process that has been observed with Mycobacterium tuberculosis [53] and Streptococcus pneumoniae pneumolysin [54]. "
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