Characterization of Chronic Cutaneous Lesions from TNF-Receptor-1-Deficient Mice Infected byLeishmania major

Abstract

Leishmania major-infected TNF receptor 1 deficient (TNFR1 KO) mice resolve parasitism but fail to resolve lesions, while wild-type mice completely heal. We investigated the cell composition, cytokine production, and apoptosis in lesions from L. major-infected TNFR1 KO and wild-type (WT) mice. Chronic lesions from L. major-infected TNFR1 KO mice presented larger number of CD8+ T and Ly6G+ cells. In addition, higher concentrations of mRNA for IFN-γ CCL2 and CCL5, as well as protein, but lower numbers of apoptotic cells, were found in lesions from TNFR1 KO mice than in WT, at late time points of infection. Our studies showed that persistent lesions in L. major-infected TNFR1 KO mice may be mediated by continuous migration of cells to the site of inflammation due to the presence of chemokines and also by lower levels of apoptosis. We suggest that this model has some striking similarities to the mucocutaneous clinical form of leishmaniasis.

Tumor Necrosis Factor Receptor-1 (p55) Deficiency Attenuates Tumor Growth and Intratumoral Angiogenesis and Stimulates CD8+ T Cell Function in Melanoma

“…Considering that development of CD4 + and CD8 + T cells is similar in WT, TNFR1 KO and TNFR2 KO [ 47 ], it is tempting to speculate that TNF-α/TNFR1 signaling may control lymphocyte migration toward sites of injury. Accordingly, lesions generated in Leishmania major -infected TNFR1 KO mice are persistent and display an increased infiltrate of CD8 + T cells [ 48 ]. Although other report demonstrated that TNFR1 KO mice are more susceptible to infection with Listeria monocytogenes [ 47 ], the role of CD8 + T cells in this process has not been examined.…”

Natural Products: Insights into Leishmaniasis Inflammatory Response

“…They promote inflammation by inducing the expression of adhesion molecules (selectin and integrin ligands) on the endothelial surface. TNF- or TNF-receptor 1- (TNFR1-) deficient mice are able to control L. major replication but develop larger lesions [ 24 , 25 ]. The role of IL-1 in leishmaniasis is controversial, as IL-1 contributes to Th1 priming at early infection but worsens the disease outcome in established infection [ 26 ].…”

Tumour necrosis factor in infectious disease

“…Most recent studies support a role for TNF in the host response to a range of bacterial parasitic and viral infections. Leishmania major ‐infected TNFR1‐deficient mice resolve parasitism but fail to resolve cutaneous lesions, in part because of impaired apoptotic clearance of inflammatory infiltrates in the healing of lesions . In Legionella pneumophilia infection, TNFR1 and TNFR2 both appear to be important in controlling infection.…”