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Abstract
SUMMARYBasic leucine zipper transcription factor 2 (Batf2) activation is detrimental in Type 1-controlled infectious diseases, demonstrated during infection with Mycobacterium tuberculosis (Mtb) and Listeria monocytogenes Lm. In Batf2-deficient mice (Batf2−/−), infected with Mtb or Lm, mice survived and displayed reduced tissue pathology compared to infected control mice. Indeed, pulmonary inflammatory macrophage recruitment, pro-inflammatory cytokines and immune effectors were also decreased during tuberculosis. This explains that batf2 mRNA predictive early biomarker found in active TB patients is increased in peripheral blood. Similarly, Lm infection in human macrophages and mouse spleen and liver also increased Batf2 expression. In striking contrast, Type 2-controlled schistosomiasis exacerbates during infected Batf2−/− mice with increased intestinal fibro-granulomatous inflammation, pro-fibrotic immune cells, and elevated cytokine production leading to wasting disease and early death. Together, these data strongly indicate that Batf2 differentially regulates Type 1 and Type 2 immunity in infectious diseases.
Highlights
Batf[2] is a transcription factor that belongs to the basic leucine zipper transcription factor family, which includes Batf and Batf3.1,2 Batf[2] is expressed in immune cells such as T cells, B cells,[3] macrophages, and dendritic cells.[4,5] Batf[2] was originally identified as an inhibitor of AP-1 via its interaction with c-JUN in cancer cells.[6]
1234567890();,: RESULTS Basic leucine zipper transcription factor 2 (Batf2)−/− mice are resistant to the hypervirulent HN878 strain of Mycobacterium tuberculosis (Mtb) with reduced acute lung inflammation In a genome-wide transcriptomics analysis, we previously reported that Batf[2] is highly induced in Mtb-infected and IFN-γ activated macrophages (M1) in vitro.[4]
Despite higher bacterial burden (105 CFUs), IFNar1−/− mice were resistant to Mtb infection by decreasing recruitment of inflammatory macrophages, chemokines, pro-inflammatory cytokines (Il1a, IL1b, Tnf, Il6) and decreased nitric oxide killing effector function
Summary
Batf[2] is a transcription factor that belongs to the basic leucine zipper transcription factor family, which includes Batf and Batf3.1,2 Batf[2] is expressed in immune cells such as T cells, B cells,[3] macrophages, and dendritic cells.[4,5] Batf[2] was originally identified as an inhibitor of AP-1 via its interaction with c-JUN in cancer cells.[6]. Batf[2] induces pro-inflammatory responses in lung recruited macrophages, leading to deleterious inflammation and TB disease progression To better define cellular infiltration in the lungs, cell populations were analyzed by flow cytometry, at 3 weeks post-infection with 100 CFU/mouse of Mtb HN878.
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