Background:  CXCL12, CCL25, and CCL28 are chemokines that play important roles in mucosal immunity by recruiting plasma cells. In particular, CCL25 and CCL28 recruit IgA-secreting cells (ASC) in the mucosal lamina propria (MLP). CXCL12 uses CXCR4 as it receptor, whereas ASC respond to CCL25 and CCL28 and migrate into the MLP via the surface receptors CCR9 (CCL25), CCR3, and CCR10 (CCL28). HIV-exposed but uninfected individuals (EU) are characterized by the presence of HIV-specific IgA in mucosal secretions. We analyzed the CXCL12 and the CCL25/28 systems in EU, as well as in healthy, HIV-unexposed controls, and HIV-infected individuals.

Methods:  CXCL12, CCL25, and CCL28 were quantified in serum and saliva, as well as in vaginal or urethral washes of 15 EU, 15 controls, and 15 HIV⁺ patients. CXCR4, CCR9, CCR3, and CCR10 expression was measured in CD3-, CD19-, and CD14-expressing peripheral blood cells of the same individuals.

Results:  CXCL12 and CCL28 were increased in serum, saliva, and vaginal and urethral washes of EU and HIV⁺ compared to the controls whereas the levels of CCL25 were comparable in all conditions measured. The percentage of CXCR4-, CCR3-, and CCR10-expressing peripheral CD19⁺ cells was similarly augmented in EU and HIV compared to controls. Interestingly, CD19⁺ cells of EU expressed a higher density of CXCR4, CCR9, and CCR10 per cell than of either HIV⁺ or HC. No differences were observed in CCR9.

Conclusions:  The CXCL12 and the CCL28 systems, but not the CCL25 circuit, are up-regulated in EU. CXCL12 favors the recruitment of plasma cells and CCL28 attracts IgA ASC in the mucosal lamina propria; in particular it has been shown recently that CCR10 is specifically expressed by IgA-secreting cells. These results could therefore explain the IgA expression that characterizes the HIV-exposed but uninfected condition.