Macrophage interactions with neutrophils regulate Leishmania major infection

FL Ribeiro-Gomes, AC Otero, NA Gomes… - The Journal of …, 2004 - journals.aai.org
FL Ribeiro-Gomes, AC Otero, NA Gomes, MCA Moniz-de-Souza, L Cysne-Finkelstein…
The Journal of Immunology, 2004journals.aai.org
Macrophages are host cells for the pathogenic parasite Leishmania major. Neutrophils die
and are ingested by macrophages in the tissues. We investigated the role of macrophage
interactions with inflammatory neutrophils in control of L. major infection. Coculture of dead
exudate neutrophils exacerbated parasite growth in infected macrophages from susceptible
BALB, but killed intracellular L. major in resistant B6 mice. Coinjection of dead neutrophils
amplified L. major replication in vivo in BALB, but prevented parasite growth in B6 mice …
Abstract
Macrophages are host cells for the pathogenic parasite Leishmania major. Neutrophils die and are ingested by macrophages in the tissues. We investigated the role of macrophage interactions with inflammatory neutrophils in control of L. major infection. Coculture of dead exudate neutrophils exacerbated parasite growth in infected macrophages from susceptible BALB, but killed intracellular L. major in resistant B6 mice. Coinjection of dead neutrophils amplified L. major replication in vivo in BALB, but prevented parasite growth in B6 mice. Neutrophil depletion reduced parasite load in infected BALB, but exacerbated infection in B6 mice. Exacerbated growth of L. major required PGE 2 and TGF-β production by macrophages, while parasite killing depended on neutrophil elastase and TNF-α production. These results indicate that macrophage interactions with dead neutrophils play a previously unrecognized role in host responses to L. major infection.
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