Interleukin 22 Inhibits Intracellular Growth of Mycobacterium tuberculosis by Enhancing Calgranulin A Expression
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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.
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IL-22 exerts direct anti-mycobacterial activity in macrophages by stimulating phagolysosomal fusion.
“whereas another Th17-derived cytokine, IL-22, exerts direct anti-mycobacterial activity in macrophages by stimulating phagolysosomal fusion.”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [106]
The effect of IL-22 on phagolysosomal fusion is traced to IL-22-mediated activation of calgranulin A with subsequent induction of Rab7 and inhibition of Rab14 expression.
“This effect could be traced back to IL-22-mediated activation of calgranulin A with subsequent induction of Rab7 and inhibition of Rab14 expression (106).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [106]
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- Authors
- Dhiman, R., Venkatasubramanian, S., Paidipally, P., Barnes, P. F., Tvinnereim, A., & Vankayalapati, R.
- Affiliations
- The University of Texas Health Science Center at Tyler (US)
- Corresponding author
- Dhiman, Rohan
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-09-16
- Volume
- 209
- Issue
- 4
- Pages
- 578-587
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC3903372
- OpenAlex
- W2111494418
- Cited by
- 68
- References
- 50
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 9 · 2020: 8 · 2019: 3 · 2018: 11 · 2017: 8 · 2016: 4 · 2015: 8 · 2014: 1 · 2013: 1
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (A1085135)
- National Institute of Allergy and Infectious Diseases (R01AI054629, AI054629, AI06366)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- IL-22, Mycobacterium tuberculosis, S100A8, phagolysosomal fusion, monocyte-derived macrophages, Rab7, Rab14
- MeSH terms
- rab7 GTP-Binding Proteins, Interleukin-22, Cells, Cultured, Humans, Interleukins, Macrophages, Mycobacterium tuberculosis, Phagocytosis, Phagosomes, Recombinant Proteins, Statistics, Nonparametric, Oligonucleotide Array Sequence Analysis, rab GTP-Binding Proteins, RNA, Small Interfering, Calgranulin A, Gene Knockdown Techniques
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