Inflammatory chemokine receptors CCR1, CCR2, CCR3 and CCR5 are essential for an optimal T cell response to influenza

Inflammatory chemokine receptors CCR1/2/3/5 (iCCRs) play an important role in the recruitment of immune cells involved in innate immune functions and orchestrating the adaptive immune response. Here we utilise an influenza A virus (IAV) challenge to investigate the combinatorial roles of the iCCRs in the anti-IAV immune response.

We did not observe any gross differences in infection-driven pathology in the absence of iCCRs. Despite iCCR deletion resulting in decreased migration of monocytes, migratory macrophages and B cells to lungs during acute IAV infection, no differences in dendritic cell numbers were observed. Whilst the total number of T cells was similar in lungs of iCCR-deficient mice, the number of IAV-specific CD4 but not CD8 T cells in the lung was strongly reduced in the absence of iCCRs. Furthermore, fewer CD4, but not CD8, T cells produced IFN-γ.

This CD4 T cell phenotype persisted into the memory stage of infection, with fewer IAV-specific and IFN-γ ⁺ CD4 but not CD8 T cells at 29 days post infection.

In conclusion, despite having no impact on dendritic cell migration between the lung and the draining lymph node, iCCR deletion is associated with an altered CD4 T cell response to IAV infection.