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Mucosal Immunol. 2019 Mar;12(2):390-402. doi: 10.1038/s41385-018-0108-2. Epub 2018 Dec 12.

Batf2 differentially regulates tissue immunopathology in Type 1 and Type 2 diseases.

Author information

1
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, 7925, South Africa.
2
Department of Pathology, University of Cape Town, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
3
Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Diseases and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
4
The Medical Research Centre, Institute of Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and Innovation, Yaoundé, Cameroon.
5
Division of Medical Microbiology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
6
Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.
7
RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
8
South African Tuberculosis Vaccine Initiative, Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, 7925, South Africa.
9
The Center for Infectious Disease Research, Seattle, WA, 98109, USA.
10
RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan. harukazu.suzuki@riken.jp.
11
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, 7925, South Africa. frank.brombacher@icgeb.org.
12
Department of Pathology, University of Cape Town, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa. frank.brombacher@icgeb.org.
13
Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Diseases and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa. frank.brombacher@icgeb.org.

Abstract

Basic 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.

PMID:
30542107
DOI:
10.1038/s41385-018-0108-2

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