Chemokines: Key Players in Innate and Adaptive Immunity

Healthy individuals initiate an immediate immune response to microbes by using a set of germline-encoded receptors that recognize common molecular patterns found on the surface of pathogens that are distinct from self-antigens. This innate immune response is the first line of defense against microorganisms in vertebrates, and constitutes the only immune response in plants and invertebrates. The innate immune system includes cellular components, as well as a host of soluble products (antimicrobial peptides, complement fragments, cytokines, and chemokines). The adaptive immune response, which provides long-lasting protection, takes days to develop and requires somatic mutations leading to the development of antigen-specific T cell receptors (cell-mediated immunity) and immunoglobulins (humoral immunity). Members of the chemokine superfamily are crucially involved in both innate and adaptive responses. We review the biological actions of the chemokine superfamily, focusing on several functions that are relevant for both immune responses, such as cell recruitment, microbicidal activity, cell activation, polarization of CD4+ T cells, and effects on structural cells. In particular, we will illustrate the central role that chemokines play in host defense, best demonstrated by the tremendous number of chemokine and chemokine receptor homologs found in microbial genomes, which deflect the immune response of the host.