Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection - PubMed (original) (raw)

Comparative Study

. 2004 Aug 16;200(4):535-40.

doi: 10.1084/jem.20040769. Epub 2004 Aug 9.

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Comparative Study

Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection

Javier A Carrero et al. J Exp Med. 2004.

Abstract

Infection with Listeria monocytogenes causes lymphocyte apoptosis that is mediated by the actions of the pore-forming virulence factor listeriolysin O (LLO). Previous work showed that activated lymphocytes were highly sensitive to LLO-induced apoptosis, whereas resting lymphocytes were less susceptible. We now show that mice deficient in the type I interferon (IFN) receptor were more resistant to Listeria infection and had less apoptotic lesions than wild-type counterparts. Furthermore, treatment of resting splenic lymphocytes with recombinant IFN-alphaA enhanced their susceptibility to LLO-induced apoptosis. Together, these data suggest that type I IFN signaling is detrimental to handling of a bacterial pathogen and may enhance the susceptibility of lymphocytes undergoing apoptosis in response to bacterial pore-forming toxins.

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Figures

Figure 1.

Figure 1.

Bacterial burden and cytokine profile of 129Sv/Ev and IFN-αβR−/− mice infected with L. monocytogenes. Mice were infected with 2.5 × 104 Listeria intraperitoneally and at the indicated days after infection (P.I.). CFUs were assessed in the spleen (A) and liver (B). Serum CBA analysis was performed on the same mice to yield serum concentrations of IL-6 (C), TNF-α (D), IFN-γ (E), and IL-12 (F). Bars represent the means ± the SEM of at least two independent experiments with a total number of five to seven mice per group.

Figure 2.

Figure 2.

Histologic analysis of 129Sv/Ev and IFN-αβR−/− mice infected with L. monocytogenes. 129Sv/Ev (A and B) and IFN-αβR−/− (C and D) mice were infected with 5 × 104 Listeria intraperitoneally and spleens were removed and stained by either hematoxylin and eosin (H&E) (A and C) or by TUNEL (B and D) 48 h later. Each panel shows one white pulp profile stained by hematoxylin and eosin and the corresponding profile stained by TUNEL. Pictures are representative profiles from five mice per group. Bars, 50 μm.

Figure 3.

Figure 3.

Annexin V/7-AAD analysis of LLO-treated lymphocytes. A cultured, resting T cell line (A, D, G, and J) and 129Sv/Ev splenocytes (B, E, H, and K) or IFN-αβR−/− splenocytes (C, F, I, and L) were either untreated (A–C), treated with 250 ng/ml LLO (D–F), or treated with 250 ng/ml LLO after 24 h of treatment with 100 U/ml IFN-αA (G–I). Cells were stained for annexin V/7-AAD. For the spleen, data is gated on CD3+ events only. The flow cytometry plots shown in A–I are representative of two to three experiments. J–L show the average result of two experiments with the cell line and three with the splenocytes, each performed in duplicate or triplicate. J–L show the percentage of annexin V+/7-AAD− cultured cells after the indicated treatments. Although their number is related with responsiveness to IFN-αA, the double positive cells taken from the spleen are not, probably because they represent a mixture of cells varying in their in vitro susceptibility. J, T cell line; K, wild-type spleen cells; L, IFN-αβR−/− spleen cells. Asterisks indicates statistical significance at a p-value of <0.0001 (*) or <0.0041 (**) by unpaired t test.

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