title: Primary mouse lung fibroblasts help macrophages to tackle Mycobacterium tuberculosis more efficiently and differentiate into myofibroblasts up on bacterial stimulation.
abstract: Keeping with their classical role in wound healing, fibroblasts of the lung take part in the resolution of tubercular granulomas. They are totally absent in nascent granulomas, but surround necrotizing granulomas, and are the majority of cells in healed granulomas. Lung fibroblasts may become infected with Mycobacterium tuberculosis (Mtb). Two previous studies suggested an immunomodulatory effect of fibroblasts on infected macrophages. In the present study, we looked at the role of primary mouse lung fibroblasts on naive or activated mouse bone marrow macrophages infected with Mtb and the effect of infection on fibroblast properties. We observed that with fibroblasts in the vicinity, infected naive macrophages restricted the bacterial growth, while activated macrophages turned more bactericidal with concomitant increase in nitrite production. Neutralizing IL-1α in fibroblast supernatant reduced the nitrite production by infected macrophages. Secretion of IL-6 and MCP-1 was down-regulated, while TNF-α was up-regulated in infected naive macrophages. In infected activated macrophages, the secretion of IL-6 was up-regulated, while that of MCP-1 and TNF-α was unaffected. The 'fibroblast effects' were enhanced when the fibroblasts too were infected. Mtb induced IL-1 secretion and pro-fibrotic responses by fibroblasts. Mtb-induced myofibroblast conversion was blocked by rapamycin suggesting cell signalling via mTOR.
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, Uttar Pradesh, India.
authors.forename: Subash Chand
authors.initials: SC
authors.lastname: Verma
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, Uttar Pradesh, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, Uttar Pradesh, India; Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, Uttar Pradesh, India. Electronic address: manju@cdri.res.in.
authors.forename: Manju Y
authors.initials: MY
authors.lastname: Krishnan
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D054884:Host-Pathogen Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000472:pathogenicity*; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Fibrotic response; Infection; Lung fibroblasts; Tuberculosis