The mucosae-associated epithelial chemokine (MEC/CCL28) modulates immunity in HIV infection

  • PLoS One. 2007 Oct 3;2(10):e969. doi: 10.1371/journal.pone.0000969.
Eleonora Castelletti  1 ,  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
Affiliations
  • 1. Department of Preclinical Sciences, Laboratorio Interdisciplinare Technologie Avanzate Vialba, University of Milano, Milano, Italy.
PMID: 17912348 DOI: 10.1371/journal.pone.0000969
Abstract

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.

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