Abstract
Immune mediators associated with human tuberculosis (TB) remain poorly defined. This study quantified levels of lung immune mediator gene expression at the time of diagnosis and during anti-TB treatment using cells obtained by induced sputum. Upon comparison to patients with other infectious lung diseases and volunteers, active pulmonary TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity. Despite the concomitant heightened levels of Th1-type mediators, immune activation may be rendered ineffectual by high levels of intracellular (SOCS and IRAK-M) and extracellular (IL-10 and TGF-βRII, IL-1Rn, and IDO) immune suppressive mediators. These modulators are a direct response to Mycobacterium tuberculosis as, by day 30 of anti-TB treatment, many suppressive factors declined to that of controls whereas most Th1-type and innate immune mediators rose above pretreatment levels. Challenge of human immune cells with M. tuberculosis in vitro up-regulated these immune modulators as well. The observed low levels of NO synthase-2 produced by alveolar macrophages at TB diagnosis, along with the heightened amounts of suppressive mediators, support the conclusion that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type and innate immunity as an immunopathological strategy. Our data highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 718-731 |
| Number of pages | 14 |
| Journal | Journal of Immunology |
| Volume | 183 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
Tuberculosis is associated with a down-modulatory lung immune response that impairs Th1-type immunity. / Almeida, Alexandre S.; Lago, Patrícia M.; Boechat, Neio; Huard, Richard C.; Lazzarini, Luiz C O; Santos, Adalberto R.; Nociari, Marcelo; Zhu, Hongxia; Perez-Sweeney, Beatriz M.; Bang, Heejung; Ni, Quanhong; Huang, Jie; Gibson, Andrea L.; Flores, Vera C.; Pecanha, Lorena R.; Kritski, Afrânio L.; Lapa E Silva, José Roberto; Ho, John L.
In: Journal of Immunology, Vol. 183, No. 1, 01.07.2009, p. 718-731.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Tuberculosis is associated with a down-modulatory lung immune response that impairs Th1-type immunity
AU - Almeida, Alexandre S.
AU - Lago, Patrícia M.
AU - Boechat, Neio
AU - Huard, Richard C.
AU - Lazzarini, Luiz C O
AU - Santos, Adalberto R.
AU - Nociari, Marcelo
AU - Zhu, Hongxia
AU - Perez-Sweeney, Beatriz M.
AU - Bang, Heejung
AU - Ni, Quanhong
AU - Huang, Jie
AU - Gibson, Andrea L.
AU - Flores, Vera C.
AU - Pecanha, Lorena R.
AU - Kritski, Afrânio L.
AU - Lapa E Silva, José Roberto
AU - Ho, John L.
PY - 2009/7/1
Y1 - 2009/7/1
N2 - Immune mediators associated with human tuberculosis (TB) remain poorly defined. This study quantified levels of lung immune mediator gene expression at the time of diagnosis and during anti-TB treatment using cells obtained by induced sputum. Upon comparison to patients with other infectious lung diseases and volunteers, active pulmonary TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity. Despite the concomitant heightened levels of Th1-type mediators, immune activation may be rendered ineffectual by high levels of intracellular (SOCS and IRAK-M) and extracellular (IL-10 and TGF-βRII, IL-1Rn, and IDO) immune suppressive mediators. These modulators are a direct response to Mycobacterium tuberculosis as, by day 30 of anti-TB treatment, many suppressive factors declined to that of controls whereas most Th1-type and innate immune mediators rose above pretreatment levels. Challenge of human immune cells with M. tuberculosis in vitro up-regulated these immune modulators as well. The observed low levels of NO synthase-2 produced by alveolar macrophages at TB diagnosis, along with the heightened amounts of suppressive mediators, support the conclusion that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type and innate immunity as an immunopathological strategy. Our data highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response.
AB - Immune mediators associated with human tuberculosis (TB) remain poorly defined. This study quantified levels of lung immune mediator gene expression at the time of diagnosis and during anti-TB treatment using cells obtained by induced sputum. Upon comparison to patients with other infectious lung diseases and volunteers, active pulmonary TB cases expressed significantly higher levels of mediators that counteract Th1-type and innate immunity. Despite the concomitant heightened levels of Th1-type mediators, immune activation may be rendered ineffectual by high levels of intracellular (SOCS and IRAK-M) and extracellular (IL-10 and TGF-βRII, IL-1Rn, and IDO) immune suppressive mediators. These modulators are a direct response to Mycobacterium tuberculosis as, by day 30 of anti-TB treatment, many suppressive factors declined to that of controls whereas most Th1-type and innate immune mediators rose above pretreatment levels. Challenge of human immune cells with M. tuberculosis in vitro up-regulated these immune modulators as well. The observed low levels of NO synthase-2 produced by alveolar macrophages at TB diagnosis, along with the heightened amounts of suppressive mediators, support the conclusion that M. tuberculosis actively promotes down-modulatory mediators to counteract Th1-type and innate immunity as an immunopathological strategy. Our data highlight the potential application of immune mediators as surrogate markers for TB diagnosis or treatment response.
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U2 - 10.4049/jimmunol.0801212
DO - 10.4049/jimmunol.0801212
M3 - Article
VL - 183
SP - 718
EP - 731
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -