Effect of chemokine receptor CX3CR1 deficiency in a murine model of respiratory syncytial virus infection - PubMed (original) (raw)

Effect of chemokine receptor CX3CR1 deficiency in a murine model of respiratory syncytial virus infection

Crystal H Johnson et al. Comp Med. 2012 Feb.

Abstract

Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory illness in infants and young children worldwide, making it a high priority for development of strategies for prevention and treatment. RSV can cause repeat infections throughout life, with serious complications in elderly and immunocompromised patients. Previous studies indicate that the RSV G protein binds through a CX3C chemokine motif to the host chemokine receptor, CX3CR1, and modulates the inflammatory immune response. In the current study, we examined the contribution of CX3CR1 to the immune response to RSV infection in mice. CX3CR1-deficient mice showed an impaired innate immune response to RSV infection, characterized by substantially decreased NK1.1(+) natural killer, CD11b(+), and RB6-8C5(+) polymorphonuclear cell trafficking to the lung and reduced IFNγ production compared with those in wildtype control mice. Leukocytes from CX3CR1-deficient mice were poorly chemotactic toward RSV G protein and CX3CL1. These results substantiate the importance of the RSV G CX3C-CX3CR1 interaction in the innate immune response to RSV infection.

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Figures

Figure 1.

Figure 1.

Expression of CX3CR1 and CX3CL1 after RSV infection. BALB/c (closed circle) and C57BL/6 mice (open square) were infected intranasally with RSV A2. (A) The time course of BAL cell recruitment after RSV infection was evaluated. The expression of (B) CX3CR1 and (C) CX3CL1 mRNA in the lungs of RSV-infected mice on days 0, 3, 5, 7 after infection is shown. (D) The concentrations of CX3CL1 in BAL-cell free supernatant were determined by ELISA. The information shown is representative data from 3 to 5 independent experiments examining 3 mice per time point (mean ± SEM; *, P < 0.05).

Figure 2.

Figure 2.

Spleen leukocytes from CX3CR1−/− mice fail to migrate to RSV G protein or CX3CL1 but not to CCL5. (A) Chemotaxis of leukocytes from CX3CR1−/− (white bars) and wildtype (WT, black bars) C57BL/6 mice to recombinant CX3CL1, purified RSV G protein, and CCL5 (RANTES) was assessed. (B) To inhibit CX3CL1- and RSV G–protein-mediated cell chemotaxis, antiCX3CR1 antibody and antiRSV G monoclonal antibody (131-2G) were added to chambers containing either CX3CL1 or RSV G protein, and the percentage inhibition of chemotaxis was determined. *, P < 0.05; n/d, not detected.

Figure 3.

Figure 3.

CX3CR1−/− mice have impaired innate cell recruitment after RSV infection. CX3CR1−/− (white bars) and wildtype (black bars) mice were infected with RSV A2. (A) The viral load in the lungs of RSV-infected mice was determined by quantitative RT-PCR. (B) BAL cell types and (C) total BAL cell numbers on day 4 after infection. The information shown is representative data from 3 to 5 independent experiments examining 3 mice per time point (mean ± SEM; *, P < 0.05).

Figure 4.

Figure 4.

CX3CR1−/− mice have impaired cytokine production after RSV infection. CX3CR1−/− (white bars) and wildtype (black bars) mice were infected with RSV A2. (A) IFNγ and (B) IL4 levels in cell-free BAL supernatant were measured by ELISA on day 6 after infection. The information shown is representative data from 3 to 5 independent experiments examining 3 mice per time point (mean ± SEM; *, P < 0.05).

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