MicroRNA-155 knockout mice are susceptible to Mycobacterium tuberculosis infection

Iwai, Hiroki; Funatogawa, Keiji; Matsumura, Kazunori; Kato-Miyazawa, Masako; Kirikae, Fumiko; Kiga, Kotaro; Sasakawa, Chihiro; Miyoshi‐Akiyama, Tohru; Kirikae, Teruo

doi:10.1016/j.tube.2015.03.006

Cited by 54 publications

(41 citation statements)

References 21 publications

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“…3E). This observation is supported by a previous study (18 mice, both during the onset of adaptive immunity and during chronic stages of infection (Fig. 3 F and G and Fig.…”

Section: Impaired Mtb Control By Mir-155supporting

confidence: 91%

MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis

Rothchild

Sissons

Shafiani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

116

106

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The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtbinfected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.

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“…3E). This observation is supported by a previous study (18 mice, both during the onset of adaptive immunity and during chronic stages of infection (Fig. 3 F and G and Fig.…”

Section: Impaired Mtb Control By Mir-155supporting

confidence: 91%

MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis

Rothchild

Sissons

Shafiani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

116

106

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“…Eight-week-old BALB/c and SCID mice were obtained from CLEA Japan, Tokyo, Japan. Bacteria were grown to mid-log phase in MycoBroth, washed twice with PBS, filtered through a 5-m Acrodisc, and adjusted to 10 5 to 10 7 CFU/ml, as previously described (11). Mice were injected intravenously with 0.2 ml of bacterial suspension.…”

Section: Ethicsmentioning

confidence: 99%

“…Bacterial strains and growth conditions. The virulent M. tuberculosis Erdman strain was obtained as previously described (11,12 Industrial, Tokyo, Japan] containing 500 mg ammonium sulfate, 500 mg L-glutamic acid, 100 mg sodium citrate, 1 mg pyridoxine, 0.5 mg biotin, 2.5 g disodium phosphate, 1 g monopotassium phosphate, 50 mg magnesium sulfate, 500 mg calcium chloride, 1 mg zinc sulfate, 850 mg NaCl, 5 g bovine serum albumin, 2 g dextrose, 3 mg catalase, and 500 mg Tween 80 per liter [pH 6.6 Ϯ 0.2]). M. tuberculosis strains were also incubated on egg-based Ogawa slant medium (Kyokuto Pharmaceutical Industrial) and Middlebrook 7H10 agar (BD Biosciences) containing 10% oleic acid-albumin-dextrose-catalase (OADC; BD Biosciences), 0.5% glycerol, and 0.05% Tween 80 (7H10/OADC).…”

mentioning

confidence: 99%

A Mutation in the 16S rRNA Decoding Region Attenuates the Virulence of Mycobacterium tuberculosis

et al. 2016

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g Mycobacterium tuberculosis contains a single rRNA operon that encodes targets for antituberculosis agents, including kanamycin. To date, only four mutations in the kanamycin binding sites of 16S rRNA have been reported in kanamycin-resistant clinical isolates. We hypothesized that another mutation(s) in the region may dramatically decrease M. tuberculosis viability and virulence. Here, we describe an rRNA mutation, U1406A, which was generated in vitro and confers resistance to kanamycin while highly attenuating M. tuberculosis virulence. The mutant showed decreased expression of 20% (n ‫؍‬ 361) of mycobacterial proteins, including central metabolic enzymes, mycolic acid biosynthesis enzymes, and virulence factors such as antigen 85 complexes and ESAT-6. The mutation also induced three proteins, including KsgA (Rv1010; 16S rRNA adenine dimethyltransferase), which closely bind to the U1406A mutation site on the ribosome; these proteins were associated with ribosome maturation and translation initiation processes. The mutant showed an increase in 17S rRNA (precursor 16S rRNA) and a decrease in the ratio of 30S subunits to the 70S ribosomes, suggesting that the U1406A mutation in 16S rRNA attenuated M. tuberculosis virulence by affecting these processes.

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“…miR-155 can modulates mycobacterial infection-induced apoptosis of macrophages (Ghorpade et al, 2012), and promotes autophagic response in macrophages and suppresses the survival of intracellular mycobacteria . miR-155-deficient mice are susceptible to M. tuberculosis infection, and died significantly earlier than wild-type mice (Iwai et al, 2015). MicroRNA let-7f is down-regulated in mycobacteria-infected macrophages, and let-7f overexpression diminishes M. tuberculosis survival and augments the production of cytokines TNF and IL-1␤ (Kumar et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

miR-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages

Liu

Wang

Jiang

et al. 2015

Molecular Immunology

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MicroRNA-155 knockout mice are susceptible to Mycobacterium tuberculosis infection

Cited by 54 publications

References 21 publications

MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis

MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis

A Mutation in the 16S rRNA Decoding Region Attenuates the Virulence of Mycobacterium tuberculosis

miR-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages

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