title: Photoconvertible pathogen labeling reveals nitric oxide control of Leishmania major infection in vivo via dampening of parasite metabolism.
abstract: The immune system can control infectious diseases through different modes of action, including direct killing or spatial confinement. Addressing how the immune system impacts pathogen biology in vivo has remained challenging. We expressed a photoconvertible fluorescent protein in pathogens in order to track their spatial dissemination in infected tissues. In addition, we developed the fluorescence recovery after photoconversion (FRAC) method in order to probe pathogen metabolic activity in vivo. Combining these two approaches in the context of Leishmania major infection of mice and pharmacologically inhibiting iNOS, we found that nitric oxide produced during the immune response to L. major reduces the metabolic activity of intracellular parasites without necessarily exerting direct killing. We propose that this chronic pressure on pathogen proliferation represents a sublethal mode of control required for ultimately resolving the infection. The ability to probe pathogen biology in response to immune defense mechanisms in vivo should create opportunities for better dissecting host-pathogen interactions.
authors.affiliation: Institut Pasteur, Dynamics of Immune Responses, 75015 Paris, France; INSERM U668, 75015 Paris, France. Electronic address: andreas.muller@pasteur.fr.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Müller
authors.forename: Salome
authors.initials: S
authors.lastname: Aeschlimann
authors.forename: Romain
authors.initials: R
authors.lastname: Olekhnovitch
authors.forename: Mariko
authors.initials: M
authors.lastname: Dacher
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Späth
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D018320:Leishmania major / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008660:Metabolism / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000276:immunology* / Q000633:toxicity*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods
chemical_list: D008164:Luminescent Proteins; D011994:Recombinant Proteins; D009569:Nitric Oxide