title: Interleukin 22 inhibits intracellular growth of Mycobacterium tuberculosis by enhancing calgranulin A expression.
abstract: Previously, we found that interleukin 22 (IL-22) inhibits intracellular growth of Mycobacterium tuberculosis in human monocyte-derived macrophages (MDMs). In the current study, we determined the mechanisms underlying these effects. We found that W7, a phagolysosomal fusion inhibitor, abrogates IL-22-dependent M. tuberculosis growth inhibition in MDMs, suggesting that IL-22 acts through enhanced phagolysosomal fusion. Our microarray analysis indicated that recombinant IL-22 (rIL-22) enhances the expression of an intracellular signaling molecule, calgranulin A. This was confirmed by real-time polymerase chain reaction, Western blot, and confocal microscopy. Calgranulin A small interfering RNA (siRNA) abrogated rIL-22-dependent growth inhibition of M. tuberculosis in MDMs. IL-22 enhanced Rab7 expression and downregulated Rab14 expression of M. tuberculosis-infected MDMs, and these effects were reversed by calgranulin A siRNA. These results suggest that M. tuberculosis growth inhibition by IL-22 depends on calgranulin A and enhanced phagolysosomal fusion, which is associated with increased Rab7 and reduced Rab14 expression.
authors.affiliation: Center for Pulmonary and Infectious Disease Control.
authors.forename: Rohan
authors.initials: R
authors.lastname: Dhiman
authors.forename: Sambasivan
authors.initials: S
authors.lastname: Venkatasubramanian
authors.forename: Padmaja
authors.initials: P
authors.lastname: Paidipally
authors.forename: Peter F
authors.initials: PF
authors.lastname: Barnes
authors.forename: Amy
authors.initials: A
authors.lastname: Tvinnereim
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Vankayalapati
mesh_terms: D040501:Calgranulin A / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006801:Humans; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D018709:Statistics, Nonparametric; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000097043:Interleukin-22
chemical_list: D040501:Calgranulin A; D007378:Interleukins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000097043:Interleukin-22; C000716463:rab7 GTP-binding proteins, human; C553411:Rab14 protein, human
keywords: Cytokine; Human; IL-22; tuberculosis
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