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iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice

(2009) PLOS PATHOGENS. 5(6).
Author
Organization
Abstract
Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2) and subsequent production of NO. Here, we show that CD11b(+) CD11c(+) Ly-6C(+) MHC-II(+) cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC) observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-gamma and MyD88 molecules with a partial contribution of TNF-alpha and TLR9. In contrast, STAT-6 deficiency enhanced iNOS-DC recruitment and activation in susceptible BALB/c mice, demonstrating a key role for IL-4 and IL-13 as negative regulators. Taken together, our results suggest that iNOS-DC represent a major class of Th1-regulated effector cell population and constitute the most frequent infected cell type during chronic Leishmania major infection phase of C57BL/6 resistant mice.
Keywords
NITRIC-OXIDE SYNTHASE, INTERFERON-GAMMA, BACTERIAL-INFECTION, IMMUNE-RESPONSES, MYD88-DEPENDENT ACTIVATION, DEFICIENT MICE, TNF-ALPHA, SUSCEPTIBILITY, EXPRESSION, PROTEIN

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Chicago
De Trez, Carl, Stefan Magez, Shizuo Akira, Bernhard Ryffel, Yves Carlier, and Eric Muraille. 2009. “iNOS-producing Inflammatory Dendritic Cells Constitute the Major Infected Cell Type During the Chronic Leishmania Major Infection Phase of C57BL/6 Resistant Mice.” Plos Pathogens 5 (6).
APA
De Trez, C., Magez, S., Akira, S., Ryffel, B., Carlier, Y., & Muraille, E. (2009). iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice. PLOS PATHOGENS, 5(6).
Vancouver
1.
De Trez C, Magez S, Akira S, Ryffel B, Carlier Y, Muraille E. iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice. PLOS PATHOGENS. 2009;5(6).
MLA
De Trez, Carl et al. “iNOS-producing Inflammatory Dendritic Cells Constitute the Major Infected Cell Type During the Chronic Leishmania Major Infection Phase of C57BL/6 Resistant Mice.” PLOS PATHOGENS 5.6 (2009): n. pag. Print.
@article{8131883,
  abstract     = {Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2) and subsequent production of NO. Here, we show that CD11b(+) CD11c(+) Ly-6C(+) MHC-II(+) cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC) observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-gamma and MyD88 molecules with a partial contribution of TNF-alpha and TLR9. In contrast, STAT-6 deficiency enhanced iNOS-DC recruitment and activation in susceptible BALB/c mice, demonstrating a key role for IL-4 and IL-13 as negative regulators. Taken together, our results suggest that iNOS-DC represent a major class of Th1-regulated effector cell population and constitute the most frequent infected cell type during chronic Leishmania major infection phase of C57BL/6 resistant mice.},
  articleno    = {e1000494},
  author       = {De Trez, Carl and Magez, Stefan and Akira, Shizuo and Ryffel, Bernhard and Carlier, Yves and Muraille, Eric},
  issn         = {1553-7366},
  journal      = {PLOS PATHOGENS},
  language     = {eng},
  number       = {6},
  pages        = {13},
  title        = {iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000494},
  volume       = {5},
  year         = {2009},
}

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