PLoS ONE (Oct 2007)

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

  • Eleonora Castelletti,
  • 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

DOI
https://doi.org/10.1371/journal.pone.0000969
Journal volume & issue
Vol. 2, no. 10
p. e969

Abstract

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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.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.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.