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


RESULTS
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.
Castelletti
Eleonora
E
Department of Preclinical Sciences, Laboratorio Interdisciplinare Technologie Avanzate Vialba, University of Milano, Milano, Italy.
Lo Caputo
Sergio
S
Kuhn
Louise
L
Borelli
Manuela
M
Gajardo
Johanna
J
Sinkala
Moses
M
Trabattoni
Daria
D
Kankasa
Chipepo
C
Lauri
Eleonora
E
Clivio
Alberto
A
Piacentini
Luca
L
Bray
Dorothy H
DH
Aldrovandi
Grace M
GM
Thea
Donald M
DM
Veas
Francisco
F
Nebuloni
Manuela
M
Mazzotta
Francesco
F
Clerici
Mario
M
D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000378:metabolism; D019742:Chemokines, CC / Q000235:genetics* / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism; D054447:Receptors, CCR10 / Q000096:biosynthesis; D054397:Receptors, CCR3 / Q000096:biosynthesis
D018941:Antigens, CD19; C414047:CCL28 protein, human; C511142:Ccl28 protein, mouse; C515707:Ccr10 protein, mouse; C515351:Ccr3 protein, mouse; D019742:Chemokines, CC; D007070:Immunoglobulin A; D054447:Receptors, CCR10; D054397:Receptors, CCR3