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M. tuberculosis infection in diabetics is associated with increased inflammatory cytokine but decreased Suppressor of cytokine signaling (SOCS)-3 responses
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  • Kiran Iqbal,
  • Muhammad Irfan,
  • Qamar Masood,
  • Maliha Yameen,
  • Nanik Ram,
  • Bushra Jamil,
  • Shoaib Rao,
  • Martin Rottenberg,
  • Zahra Hasan
Kiran Iqbal
Aga Khan University
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Muhammad Irfan
Aga Khan University
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Qamar Masood
Aga Khan University
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Maliha Yameen
Aga Khan University
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Nanik Ram
Aga Khan University
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Bushra Jamil
Aga Khan University
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Shoaib Rao
Aga Khan University
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Martin Rottenberg
Karolinska Institutet
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Zahra Hasan
The Aga Khan University
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Abstract

Introduction Tuberculosis (TB) infections and latent Mycobacterium tuberculosis (MTB) infection (LTBi) remain prevalent globally. Type 2 diabetes mellitus (DM) worsens TB outcomes but the immune mechanisms that cause this are not yet clear. We investigated a role of suppressor of cytokine signaling molecules (SOCS1 and SOC3) in regulating host cytokine responses in the diabetic host infected with MTB. Materials and Methods We studied peripheral blood cells from health endemic controls (EC), LTBi cases, diabetics with and without LTBi and TB patients. Mycobacterial antigen-stimulated cytokine secretion was determined using the Th1/Th2 11 plex cytokine assay. Antigen-induced gene expression of IFNγ, TNFα, IL6 and SOCS3 was determined by reverse-transcription PCR. Results Purified protein derivative (PPD) antigen stimulation induced higher levels of, IL-6, IL-2, TNFα and GM-CSF levels in DM-LTB as compared with EC and LTB cases. IL-13 levels were raised in DM-LTB cases as compared with DM cases. PPD-induced IFNγ and IL-6 transcripts were raised in DM-LTBi as compared with EC. TNFα mRNA levels were raised in DM-LTBi as compared with LTBi. SOCS3 mRNA levels were reduced in DM-LTBi as compared with LTBi. SOCS3 transcripts were higher in LTBi as compared with EC and TB groups. Discussion We found co-occurrence of LTBi with DM to be associated with an increased release of proinflammatory IL-6, IL-2 and TNF-α but reduced SOCS3 mRNA levels. SOCS3 protects against MTB infection therefore, reduced levels in DM-LTB may be contribute to progression from LTBi to active TB in individuals infected with MTB.