CD23 mediates antimycobacterial activity of human macrophages.
Engagement of surface receptors contributes to the antimicrobial activity of human immune cells. We show here that infection of human monocyte-derived macrophages (MDM) with live Mycobacterium avium induced the expression of CD23 on their membrane. Subsequent cross-linking of surface CD23 by appropriate ligands induced a dose-dependent antibacterial activity of MDM and the elimination of most infected cells. The stimulation of inducible nitric oxide synthase-dependent generation of NO from MDM after CD23 activation played a major role during their anti-M. avium activity. CD23 activation also induced tumor necrosis factor alpha (TNF-alpha) production from MDM. Mycobacteria reduction was partially inhibited by the addition of neutralizing anti-TNF-alpha antibody to cell cultures without affecting NO levels, which suggested the role of this cytokine for optimal antimicrobial activity. Finally, interleukin-10, a Th2 cytokine known to downregulate CD23 pathway, is shown to decrease NO generation and mycobacteria elimination by macrophages. Therefore, (i) infection with M. avium promotes functional surface CD23 expression on human macrophages and (ii) subsequent signaling of this molecule contributes to the antimicrobial activity of these cells through an NO- and TNF-alpha-dependent pathway. This study reveals a new human immune response mechanism to counter mycobacterial infection involving CD23 and its related ligands.
Mossalayi
M Djavad
MD
Laboratoire d'Immunologie et Parasitologie, Faculté de Pharmacie, Université Victor Segalen-Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France. djavad.mossalayi@u-bordeaux2.fr
Vouldoukis
Ioannis
I
Mamani-Matsuda
Maria
M
Kauss
Tina
T
Guillon
Jean
J
Maugein
Jeanne
J
Moynet
Daniel
D
Rambert
Jérôme
J
Desplat
Vanessa
V
Mazier
Dominique
D
Vincendeau
Philippe
P
Malvy
Denis
D
D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D050296:Microbial Viability; D009162:Mycobacterium avium / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D017455:Receptors, IgE / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide