Mucosal Immunol. 2025 May 23:S1933-0219(25)00052-2. doi: 10.1016/j.mucimm.2025.05.005. Online ahead of print.
ABSTRACT
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. iCCR deletion resulted in decreased numbers of some antigen-presenting cell types in the lung (B cells, DC1s, monocytes and inflammatory macrophages), though cell numbers in the draining lymph node were not affected. 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 limited impact on antigen-presenting cell migration between the lung and the draining lymph node, iCCR deletion is associated with an altered CD4 T cell response to IAV infection.
PMID:40414601 | DOI:10.1016/j.mucimm.2025.05.005