The role of cytokines in mycobacterial infection

ABSTRACT With a view to exploring the role of transforming growth factor β (TGF-β) during mycobacterial infection, recombinant clones of bacillus Calmette-Guérin (BCG) were engineered to express the natural antagonist of TGF-β, latency-activated peptide (LAP). Induction of TGF-β activity was reduced when macrophages were infected with BCG expressing the LAP construct (LAP-BCG). There was a significant reduction in the growth of LAP-BCG in comparison to that of control BCG following intravenous infection in a mouse model. The enhanced control of mycobacterial replication was associated with an increase in the production of gamma interferon by splenocytes challenged during the acute stage of infection but with a diminished recall response assessed after 13 weeks. Organ weight and hydroxyproline content, representing tissue pathology, were also lower in mice infected with LAP-BCG. The results are consistent with the hypothesis that TGF-β has a detrimental effect on mycobacterial immunity. While a reduction in TGF-β activity augments the initial response to BCG vaccination, early bacterial clearance may adversely affect the induction of a long-term memory response by LAP-BCG.

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Role of Interleukin (IL)-1 Type 1 Receptor in Mycobacterial Infection

Microbiology and Immunology ◽

10.1111/j.1348-0421.2001.tb01310.x ◽

2001 ◽

Vol 45 (11) ◽

pp. 743-750 ◽

Cited By ~ 53

Author(s):

Isamu Sugawara ◽

Hiroyuki Yamada ◽

Shucheng Hua ◽

Satoru Mizuno

Keyword(s):

Mycobacterial Infection

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Mitofusin 2-Deficiency Suppresses Mycobacterium tuberculosis Survival in Macrophages

Cells ◽

10.3390/cells8111355 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1355 ◽

Cited By ~ 3

Author(s):

Junghwan Lee ◽

Ji-Ae Choi ◽

Soo-Na Cho ◽

Sang-Hun Son ◽

Chang-Hwa Song

Keyword(s):

Mycobacterium Tuberculosis ◽

Molecular Mechanisms ◽

Defense Mechanism ◽

Mitochondrial Fission ◽

Mycobacterial Infection ◽

Mitofusin 2 ◽

Unstimulated Control ◽

Host Defense Mechanism ◽

Important Host

Apoptosis is an important host defense mechanism against mycobacterial infection. However, the molecular mechanisms regulating apoptosis during mycobacterial infection are not well known. Recent reports suggest that bacterial infection regulates mitochondrial fusion and fission in various ways. Here, we investigated the role of mitochondria in Mycobacterium tuberculosis (Mtb)-infected macrophages. Mtb H37Rv (Rv) infection induced mitofusin 2 (MFN2) degradation, leading to mitochondrial fission. Interestingly, Mtb H37Ra (Ra) infection induced significantly greater mitochondrial fragmentation than Rv infection. Mtb-mediated Parkin, an E3 ubiquitin ligase, contributed to the degradation of MFN2. To evaluate the role of endoplasmic reticulum stress in the production of Parkin during Mtb infection, we analyzed Parkin production in 4-phenylbutyric acid (4-PBA)-pretreated macrophages. Pretreatment with 4-PBA reduced Parkin production in Mtb-infected macrophages. In contrast, the level of MFN2 production recovered to a level similar to that of the unstimulated control. In addition, Ra-infected macrophages had reduced mitochondrial membrane potential (MMP) compared to those infected with Rv. Interestingly, intracellular survival of mycobacteria was decreased in siMFN2-transfected macrophages; in contrast, overexpression of MFN2 in macrophages increased Mtb growth compared with the control.

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Neutralization or Absence of the Interleukin-23 Pathway Does Not Compromise Immunity to Mycobacterial Infection

Infection and Immunity ◽

10.1128/iai.00621-06 ◽

2006 ◽

Vol 74 (11) ◽

pp. 6092-6099 ◽

Cited By ~ 54

Author(s):

Alissa A. Chackerian ◽

Shi-Juan Chen ◽

Scott J. Brodie ◽

Jeanine D. Mattson ◽

Terrill K. McClanahan ◽

...

Keyword(s):

Immune Response ◽

Secondary Infection ◽

Mycobacterial Infection ◽

Effective Control ◽

Bacterial Burden ◽

Wild Type ◽

Interleukin 23 ◽

Deficient Mice ◽

Stimulation Of

ABSTRACT Interleukin-23 (IL-23), a member of the IL-12 family, is a heterodimeric cytokine that is composed of the p40 subunit of IL-12 plus a unique p19 subunit. IL-23 is critical for autoimmune inflammation, in part due to its stimulation of the proinflammatory cytokine IL-17A. It is less clear, however, if IL-23 is required during the immune response to pathogens. We examined the role of IL-23 during Mycobacterium bovis BCG infection. We found that IL-23 reduces the bacterial burden and promotes granuloma formation when IL-12 is absent. However, IL-23 does not contribute substantially to host resistance when IL-12 is present, as the ability to control bacterial growth and form granulomata is not affected in IL-23p19-deficient mice and mice treated with a specific anti-IL-23p19 antibody. IL-23p19-deficient mice are also able to mount an effective memory response to secondary infection with BCG. While IL-23p19-deficient mice do not produce IL-17A, this cytokine is not necessary for effective control of infection, and antibody blocking of IL-17A in both wild-type and IL-12-deficient mice also has little effect on the bacterial burden. These data suggest that IL-23 by itself does not play an essential role in the protective immune response to BCG infection; however, the presence of IL-23 can partially compensate for the absence of IL-12. Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection.

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Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

The Journal of Immunology ◽

10.4049/jimmunol.0903332 ◽

2010 ◽

Vol 184 (8) ◽

pp. 4414-4422 ◽

Cited By ~ 251

Author(s):

Yuko Okamoto Yoshida ◽

Masayuki Umemura ◽

Ayano Yahagi ◽

Rebecca L. O’Brien ◽

Koichi Ikuta ◽

...

Keyword(s):

Essential Role ◽

Mycobacterial Infection

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The role of follicular helper T cells in mycobacterial infection

Frontiers in Immunology ◽

10.3389/conf.fimmu.2013.02.00988 ◽

2013 ◽

Vol 4 ◽

Author(s):

Shimohakamada Yoko ◽

Tamura Toshiki ◽

Makino Masahiko ◽

Nutt Stephen

Keyword(s):

T Cells ◽

Mycobacterial Infection ◽

Helper T Cells ◽

Follicular Helper T Cells ◽

Follicular Helper

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Deciphering the role of a unique methyltransferase in Mycobacterial infection

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.07572 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Anshu Rani ◽

Prajna Tripathi ◽

P. Manjunath ◽

Seyed Ehtesham Hasnain ◽

Nasreen Z. Ehtesham

Keyword(s):

Mycobacterial Infection

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466: Role of itaconate in nontuberculous mycobacterial infection in cystic fibrosis

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(21)01890-7 ◽

2021 ◽

Vol 20 ◽

pp. S220-S221

Author(s):

P. Breen ◽

J. Rothman ◽

L. Kalikin ◽

J. LiPuma ◽

L. Caverly

Keyword(s):

Cystic Fibrosis ◽

Mycobacterial Infection ◽

Nontuberculous Mycobacterial Infection

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Infection-induced miR-126 suppresses tsc1- and cxcl12a-dependent permissive macrophages during mycobacterial infection

10.1101/2021.10.07.463594 ◽

2021 ◽

Author(s):

Kathryn Wright ◽

Kumudika de Silva ◽

Karren M. Plain ◽

Auriol C. Purdie ◽

Warwick J. Britton ◽

...

Keyword(s):

Immune Response ◽

Detrimental Effect ◽

Mycobacterial Infection ◽

Protective Role ◽

Zebrafish Embryos ◽

Zebrafish Model ◽

Effector Pathways ◽

The Impact ◽

Mtor Signalling

AbstractRegulation of host microRNA (miRNA) expression is a contested node that controls the host immune response to mycobacterial infection. The host must overcome concerted subversive efforts of pathogenic mycobacteria to launch and maintain a protective immune response. Here we examine the role of miR-126 in the zebrafish model of Mycobacterium marinum infection and identify a protective role for this infection-induced miRNA through multiple effector pathways. Specifically, we analyse the impact of the miR-126 knockdown-induced tsc1a and cxcl12a/ccl2/ccr2 signalling axes during early host-M. marinum interactions. We find a strong detrimental effect of tsc1a upregulation that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death despite dramatically higher recruitment of macrophages to the site of infection. We demonstrate that infection-induced miR-126 suppresses tsc1 and cxcl12a expression thus improving macrophage function early in infection, partially through activation of mTOR signalling and strongly through preventing the recruitment of Ccr2+ permissive macrophages, resulting in the recruitment of protective tnfa-expressing macrophages. Together our results demonstrate an important role for infection-induced miR-126 in shaping an effective immune response to M. marinum infection in zebrafish embryos.

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