Photoconvertible pathogen labeling reveals nitric oxide control of leishmania major infection in vivo via dampening of parasite metabolism

Andreas J. Müller, Salome Aeschlimann, Romain Olekhnovitch, Mariko Dacher, Gerald F. Späth, Philippe Bousso

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)460-467
Number of pages8
JournalCell Host and Microbe
Volume14
Issue number4
DOIs
Publication statusPublished - 2013 Oct 16
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

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