Interleukin 22 Inhibits Intracellular Growth of Mycobacterium tuberculosis by Enhancing Calgranulin A Expression

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...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of infectious diseases 2014-02, Vol.209 (4), p.578-587
Main Authors:	Dhiman, Rohan, Venkatasubramanian, Sambasivan, Paidipally, Padmaja, Barnes, Peter F., Tvinnereim, Amy, Vankayalapati, Ramakrishna
Format:	Article
Language:	eng
Subjects:	BACTERIA Bacteriology Biological and medical sciences Calgranulin A - biosynthesis Calgranulin A - genetics Calgranulin A - immunology Cells, Cultured Fundamental and applied biological sciences. Psychology Gene expression Gene Knockdown Techniques Humans Infectious diseases Interleukin-22 Interleukins Interleukins - deficiency Interleukins - genetics Interleukins - immunology Interleukins - pharmacology Macrophages Macrophages - immunology Macrophages - microbiology Major and Brief Reports Medical sciences Microbiology Miscellaneous Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - growth & development Mycobacterium tuberculosis - immunology Natural killer cells Oligonucleotide Array Sequence Analysis Phagocytosis - immunology Phagosomes Phagosomes - immunology Phagosomes - microbiology Proteins rab GTP-Binding Proteins - metabolism rab7 GTP-Binding Proteins Recombinant Proteins - immunology Recombinant Proteins - pharmacology RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNA, Small Interfering - pharmacology Small interfering RNA Statistics, Nonparametric T lymphocytes Tuberculosis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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 Rabl4 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.
ISSN:	0022-1899 1537-6613