Tumour necrosis factor (TNF)-mediated NF-κB activation facilitates cellular invasion of non-professional phagocytic epithelial cell lines by Trypanosoma cruzi

Abstract

SummaryAt the site of infection, pro-inflammatory cytokines locally produced by macrophages infected with Trypanosoma cruzi can activate surrounding nonprofessional phagocytes such as fibroblasts, epithelial and endothelial cells, which can be further invaded by the parasite. The effect of secreted soluble factors on the invasion of these cells remains, however, to be established. We show here that two epithelial cell lines become significantly susceptible to the infection by the Y strain of T. cruzi after tumour necrosis factor (TNF) treatment. The increase in the invasion was correlated with the increasing concentration of recombinant TNF added to cultures of HEK293T or LLC-MK2 cells. Supernatants taken from PMA-differentiated human monocytes infected with T. cruzi also increased the permissiveness of epithelial cells to subsequent infection with the parasite, which was inhibited by a TNF monoclonal antibody. Furthermore, the permissiveness induced by TNF was inhibited by TPCK, and led to significant decrease in the number of intracellular parasites, providing evidence that activation of NF-kB induced by TNF favours the invasion of the epithelial cell lines by T. cruzi through yet an unidentified mechanism. Our data indicate that soluble factors released from macrophages early in the infection favours T. cruzi invasion of non-professional phagocytic cells.

NFκB activation in cutaneous lesions of leprosy is associated with development of multibacillary infection

“…NFκB activation and its associated transcription modulation might be one of various bacillary adaptive mechanisms to allow chronic infection, which may in turn result in less effective host immunity. For example, if the inflammatory status mediated by NFκB in MB leprosy is not efficient enough to destroy M. leprae , this could even stimulate phagocytosis and consequent intracellular infection, similar to what has been reported with Trypanosoma cruzi ,13 where microorganism invasion and survival is favored by NFκB activation induced by TNFα. Apoptosis has been shown to be more frequent in PB than in MB, suggesting a possible mechanism for containing bacillary multiplication 14,15…”

Host Cell Poly(ADP-Ribose) Glycohydrolase Is Crucial for Trypanosoma cruzi Infection Cycle

“…ROS, either through direct modulation of cytosolic NF-κB or via PARP-1-dependent pADPr modification of p65-interacting nuclear proteins, contribute to cytokine gene expression and could be pointing out a link between ROS and inflammatory responses providing a clue to the pathomechanism of sustained inflammation in Chagas’ disease. Moreover, Pinto et al [36] show that the TNF/NF-kB axis participates in T. cruzi invasion of non-professional phagocytic epithelial cell lines, resulting in increased number of intracellular parasites, leading to the conclusion that NF-κB activation in non-immune cells elicited by paracrine factors released by immune cells represents a mechanism by which T.…”

Transsulfuration is an active pathway for cysteine biosynthesis in Trypanosoma rangeli

“…T. cruzi culture-derived trypomastigotes and amastigotes were obtained from THP-1 differentiated macrophage-like cells (ATCC) infected with Y strain metacyclic trypomastigotes [18]. Briefly, THP-1 cells (ATCC) were cultured in RPMI 1640 medium supplemented with 10% FBS at 37°C in a 5% CO 2 atmosphere and transformed to adherent macrophages using phorbol myristate acetate (50 ng/mL) for 72 h at 37°C and 5% CO 2 prior to experiments.…”