The Mucosae-Associated Epithelial Chemokine (MEC/CCL28) Modulates Immunity in HIV Infection
Lo Caputo, Sergio
Bray, Dorothy H.
Aldrovandi, Grace M.
Thea, Donald M.
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Citation (published version)Castelletti, Eleonora, Sergio Lo Caputo, Louise Kuhn, Manuela Borelli, Johanna Gajardo, Moses Sinkala, Daria Trabattoni, Chipepo Kankasa, Eleonora Lauri, Alberto Clivio, Luca Piacentini, Dorothy H. Bray, Grace M. Aldrovandi, Donald M. Thea, Francisco Veas, Manuela Nebuloni, Francesco Mazzotta, Mario Clerici. "The Mucosae-Associated Epithelial Chemokine (MEC/CCL28) Modulates Immunity in HIV Infection" PLoS ONE 2(10):e969. (2007)
BACKGROUND. CCL28 (MEC) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC) in the mucosal lamina propria (MLP). Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model. METHODOLOGY/FINDINGS. CCL28 was augmented in breast milk (BM) plasma and saliva of HIV-infected and –exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1) CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2) gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28. CONCLUSIONS. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.