Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism.
Interleukin (IL)-32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system.In the present study, freshly obtained human peripheral blood mononuclea...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2006-08-01
|
| Series: | PLoS Medicine |
| Online Access: | http://europepmc.org/articles/PMC1539091?pdf=render |
| _version_ | 1818201989839847424 |
|---|---|
| author | Mihai G Netea Tania Azam Eli C Lewis Leo A B Joosten Maorong Wang Dennis Langenberg Xianzhong Meng Edward D Chan Do-Young Yoon Tom Ottenhoff Soo-Hyun Kim Charles A Dinarello |
| author_facet | Mihai G Netea Tania Azam Eli C Lewis Leo A B Joosten Maorong Wang Dennis Langenberg Xianzhong Meng Edward D Chan Do-Young Yoon Tom Ottenhoff Soo-Hyun Kim Charles A Dinarello |
| author_sort | Mihai G Netea |
| collection | DOAJ |
| description | Interleukin (IL)-32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system.In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR) agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor alpha and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-gamma (IFNgamma); endogenous IFNgamma is, in turn, dependent on M. tuberculosis-induced IL-18 via caspase-1.In conclusion, IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFNgamma. |
| first_indexed | 2024-12-12T03:02:19Z |
| format | Article |
| id | doaj.art-23fe7a68b4c34489b681253b160b1071 |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-12T03:02:19Z |
| publishDate | 2006-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-23fe7a68b4c34489b681253b160b10712022-12-22T00:40:36ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762006-08-0138e27710.1371/journal.pmed.0030277Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism.Mihai G NeteaTania AzamEli C LewisLeo A B JoostenMaorong WangDennis LangenbergXianzhong MengEdward D ChanDo-Young YoonTom OttenhoffSoo-Hyun KimCharles A DinarelloInterleukin (IL)-32 is a newly described proinflammatory cytokine that seems likely to play a role in inflammation and host defense. Little is known about the regulation of IL-32 production by primary cells of the immune system.In the present study, freshly obtained human peripheral blood mononuclear cells were stimulated with different Toll-like receptor (TLR) agonists, and gene expression and synthesis of IL-32 was determined. We demonstrate that the TLR4 agonist lipopolysaccharide induces moderate (4-fold) production of IL-32, whereas agonists of TLR2, TLR3, TLR5, or TLR9, each of which strongly induced tumor necrosis factor alpha and IL-6, did not stimulate IL-32 production. However, the greatest amount of IL-32 was induced by the mycobacteria Mycobacterium tuberculosis and M. bovis BCG (20-fold over unstimulated cells). IL-32-induced synthesis by either lipopolysaccharide or mycobacteria remains entirely cell-associated in monocytes; moreover, steady-state mRNA levels are present in unstimulated monocytes without translation into IL-32 protein, similar to other cytokines lacking a signal peptide. IL-32 production induced by M. tuberculosis is dependent on endogenous interferon-gamma (IFNgamma); endogenous IFNgamma is, in turn, dependent on M. tuberculosis-induced IL-18 via caspase-1.In conclusion, IL-32 is a cell-associated proinflammatory cytokine, which is specifically stimulated by mycobacteria through a caspase-1- and IL-18-dependent production of IFNgamma.http://europepmc.org/articles/PMC1539091?pdf=render |
| spellingShingle | Mihai G Netea Tania Azam Eli C Lewis Leo A B Joosten Maorong Wang Dennis Langenberg Xianzhong Meng Edward D Chan Do-Young Yoon Tom Ottenhoff Soo-Hyun Kim Charles A Dinarello Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. PLoS Medicine |
| title | Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. |
| title_full | Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. |
| title_fullStr | Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. |
| title_full_unstemmed | Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. |
| title_short | Mycobacterium tuberculosis induces interleukin-32 production through a caspase- 1/IL-18/interferon-gamma-dependent mechanism. |
| title_sort | mycobacterium tuberculosis induces interleukin 32 production through a caspase 1 il 18 interferon gamma dependent mechanism |
| url | http://europepmc.org/articles/PMC1539091?pdf=render |
| work_keys_str_mv | AT mihaignetea mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT taniaazam mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT eliclewis mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT leoabjoosten mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT maorongwang mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT dennislangenberg mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT xianzhongmeng mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT edwarddchan mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT doyoungyoon mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT tomottenhoff mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT soohyunkim mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism AT charlesadinarello mycobacteriumtuberculosisinducesinterleukin32productionthroughacaspase1il18interferongammadependentmechanism |