Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages

MAFB, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, has been identified as a candidate gene for early tuberculosis (TB) onset in Thai and Japanese populations. Here, we investigated the genome-wide transcriptional profiles of MAFB-knockdown (KD) macrophages infected with Mycobacter...

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Main Authors: Haruka Hikichi, Shintaro Seto, Keiko Wakabayashi, Minako Hijikata, Naoto Keicho
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2022.962306/full
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author Haruka Hikichi
Haruka Hikichi
Shintaro Seto
Keiko Wakabayashi
Minako Hijikata
Naoto Keicho
Naoto Keicho
author_facet Haruka Hikichi
Haruka Hikichi
Shintaro Seto
Keiko Wakabayashi
Minako Hijikata
Naoto Keicho
Naoto Keicho
author_sort Haruka Hikichi
collection DOAJ
description MAFB, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, has been identified as a candidate gene for early tuberculosis (TB) onset in Thai and Japanese populations. Here, we investigated the genome-wide transcriptional profiles of MAFB-knockdown (KD) macrophages infected with Mycobacterium tuberculosis (Mtb) to highlight the potential role of MAFB in host immunity against TB. Gene expression analysis revealed impaired type I and type II interferon (IFN) responses and enhanced oxidative phosphorylation in MAFB-KD macrophages infected with Mtb. The expression of inflammatory chemokines, including IFN-γ-inducible genes, was confirmed to be significantly reduced by knockdown of MAFB during Mtb infection. A similar effect of MAFB knockdown on type I and type II IFN responses and oxidative phosphorylation was also observed when Mtb-infected macrophages were activated by IFN-γ. Taken together, our results demonstrate that MAFB is involved in the immune response and metabolism in Mtb-infected macrophages, providing new insight into MAFB as a candidate gene to guide further study to control TB.
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spelling doaj.art-6b88a58d7d8c49e38f3b53ae544327d32022-12-22T03:43:43ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-11-011310.3389/fmicb.2022.962306962306Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophagesHaruka Hikichi0Haruka Hikichi1Shintaro Seto2Keiko Wakabayashi3Minako Hijikata4Naoto Keicho5Naoto Keicho6Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, JapanDepartment of Basic Mycobacteriosis, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, JapanDepartment of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, JapanDepartment of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, JapanDepartment of Basic Mycobacteriosis, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanVice Director, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, JapanMAFB, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, has been identified as a candidate gene for early tuberculosis (TB) onset in Thai and Japanese populations. Here, we investigated the genome-wide transcriptional profiles of MAFB-knockdown (KD) macrophages infected with Mycobacterium tuberculosis (Mtb) to highlight the potential role of MAFB in host immunity against TB. Gene expression analysis revealed impaired type I and type II interferon (IFN) responses and enhanced oxidative phosphorylation in MAFB-KD macrophages infected with Mtb. The expression of inflammatory chemokines, including IFN-γ-inducible genes, was confirmed to be significantly reduced by knockdown of MAFB during Mtb infection. A similar effect of MAFB knockdown on type I and type II IFN responses and oxidative phosphorylation was also observed when Mtb-infected macrophages were activated by IFN-γ. Taken together, our results demonstrate that MAFB is involved in the immune response and metabolism in Mtb-infected macrophages, providing new insight into MAFB as a candidate gene to guide further study to control TB.https://www.frontiersin.org/articles/10.3389/fmicb.2022.962306/fullMycobacterium tuberculosismacrophageMAFBinterferon responseRNA sequencinggene set enrichment analysis
spellingShingle Haruka Hikichi
Haruka Hikichi
Shintaro Seto
Keiko Wakabayashi
Minako Hijikata
Naoto Keicho
Naoto Keicho
Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages
Frontiers in Microbiology
Mycobacterium tuberculosis
macrophage
MAFB
interferon response
RNA sequencing
gene set enrichment analysis
title Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages
title_full Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages
title_fullStr Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages
title_full_unstemmed Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages
title_short Transcription factor MAFB controls type I and II interferon response-mediated host immunity in Mycobacterium tuberculosis-infected macrophages
title_sort transcription factor mafb controls type i and ii interferon response mediated host immunity in mycobacterium tuberculosis infected macrophages
topic Mycobacterium tuberculosis
macrophage
MAFB
interferon response
RNA sequencing
gene set enrichment analysis
url https://www.frontiersin.org/articles/10.3389/fmicb.2022.962306/full
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