Loss of TNF signaling facilitates the development of a novel Ly-6C(low) macrophage population permissive for Leishmania major infection

Fromm, Phillip D., Kling, Jessica, Mack, Matthias, 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.

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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.

Item ID: 22621
Item Type: Article (Research - C1)
ISSN: 1550-6606
Date Deposited: 01 Aug 2012 09:28
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111799 Public Health and Health Services not elsewhere classified @ 33%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920404 Disease Distribution and Transmission (incl. Surveillance and Response) @ 33%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920120 Zoonoses @ 33%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 34%
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