Intracellular Signalling Pathways Induced by Chemokines in Natural Killer Cells

Chemokines are small peptides involved in the recruitment of various cell types into inflammatory sites. They are divided into four sub-families depending on the presence of amino acids separating the cysteine residues in their N-terminal region. These are the α (CXC), β (CC), γ (C) and δ (CX 3C) chemokines. In addition, five CXC chemokine (CXCR1–5), nine CC chemokine (CCR1–9), one C chemokine (XCR1) and one CX 3C chemokine (CX 3CR1) receptors have been identified. These receptors belong to the seven transmembrane spanning domain family, and are coupled to the heterotrimeric guanine nucleotide binding (G) proteins. Chemokines activate various immune cells, and in particular the anti-viral/anti-tumour effectors, the natural killer (NK) cells by activating members of the heterotrimeric G proteins. The importance of the family of chemokines is highlighted by the ability of its members to inhibit the replication of HIV-1 strains in CD4 + cells, where chemokine receptors act as HIV-1 co-receptors. This review discusses the intracellular signalling pathways induced by chemokines in NK and other cell types, and the relationships to HIV-1 signalling in these cells.