Loss of TNF Signaling Facilitates the Development of a Novel Ly-6C(low) Macrophage Population Permissive for Leishmania major Infection

Fromm, Phillip D. and Kling, Jessica and Mack, Matthias and Sedgwick, Jonathon D. and Koerner, Heinrich (2012) Loss of TNF Signaling Facilitates the Development of a Novel Ly-6C(low) Macrophage Population Permissive for Leishmania major Infection. JOURNAL OF IMMUNOLOGY, 188 (12). pp. 6258-6266. ISSN 0022-1767,

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Abstract

In the absence of TNF, the normally resistant C57BL/6 (B6.WT) strain develops a fatal, progressive form of leishmaniasis after infection with Leishmania major. It is not yet understood which TNF activity or the lack thereof is responsible for the dramatic progression of leishmaniasis in TNF-negative (B6.TNF-/-) mice. To elucidate the underlying mechanisms resulting in the fatal outcome of L. major infection in this gene-deficient mouse strain, we analyzed the monocytic component of the inflammatory infiltrate in the draining popliteal lymph node and the site of the infection using multicolor flow cytometry. The leukocytic infiltrate within the draining lymph node and footpad of B6. TNF-/- mice resembled that of B6. WT mice over the first 2 wk of cutaneous L. major infection. Thereafter, the B6. TNF-/- mice showed an increase of CD11c(+)Ly-6C(+)CCR2(+) monocytic dendritic cells within the popliteal lymph node in comparison with B6.WT mice. This increase of inflammatory dendritic cells was paired with the accumulation of a novel CD11b(+)Ly-6C(low)CCR2(low) population that was not present in B6. WT mice. This B6.TNF-/-- and B6.TNFR1(-/-)-specific cell population was CD115(+)Ly-6G(-)iNOS(-), not apoptotic, and harbored large numbers of parasites. The Journal of Immunology, 2012, 188: 6258-6266.

Item Type: Article
Uncontrolled Keywords: TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; PROGRAMMED CELL-DEATH; DENDRITIC CELLS; BACTERIAL-INFECTION; BLOOD MONOCYTES; FACTOR-ALPHA; IFN-GAMMA; CUTANEOUS LEISHMANIASIS; MURINE LEISHMANIASIS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 11 May 2020 11:57
Last Modified: 11 May 2020 11:57
URI: https://pred.uni-regensburg.de/id/eprint/18578

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