Pattern and diversity of cytokine production differentiates between <i>Mycobacterium tuberculosis</i> infection and disease

Sutherland, Jayne S.; Adetifa, Ifedayo; Hill, Philip C.; Adegbola, Richard A.; Ota, Martin O. C.

doi:10.1002/eji.200838693

Cited by 192 publications

(186 citation statements)

References 27 publications

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“…The findings and interpretation are similar to a report from the Gambia [19], also showing that HIV-uninfected TB patients had significantly higher levels of IFN-g/TNF/IL-2 CD4 1 T cells compared with healthy household contacts; however, the Gambian study [19] also found higher numbers of CD4 1 and CD8 1 T cells in active TB patients that were TNF single positive, and a significantly increased proportion of IL-2 single positive CD4 1 and CD8 1 T cells in PBMC from the household contact group in response to both PPD and ESAT-6/CFP-10 stimulation. In the Caccamo et al study [18] TNF single positive T cells were not analysed, while the IL-2 single positive response was not different between the TB and LTBI groups.…”

supporting

confidence: 90%

Polyfunctional T cells in human tuberculosis

Wilkinson

2010

Eur J Immunol

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Studies of chronic viral infections have highlighted the phenotypic and functional heterogeneity of antigen-specific T cells and suggested that polyfunctional T cells that secrete multiple cytokines and are able to proliferate on encounter with antigen are more likely than single cytokine secretors to represent correlates of protective immunity. These findings have prompted the evaluation of such T-cell responses in chronic bacterial infections, such as tuberculosis (TB). A number of studies in humans suggested that polyfunctional T cells may indeed be involved in mediating protection in TB; however, studies that question these findings are also emerging, including a study published in this issue of the European Journal of Immunology. These differing findings highlight the difficulties of studying human immunity to TB and the need for polyfunctional T cells to be evaluated in longitudinal studies as opposed to case-control analyses.

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supporting

confidence: 90%

Polyfunctional T cells in human tuberculosis

Wilkinson

2010

Eur J Immunol

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“…Furthermore, an increase of IL-17A-producing TCR gd T cells was reported in peripheral blood of patients with tuberculosis (51). In contrast, a decrease of mycobacterial Ag-specific IL-17A-producing CD4 + T cells was reported in patients with tuberculosis (49,52). The observations suggest that contact with mycobacteria induces human IL-17A-producing TCR ab or TCR gd T cells, but the mycobacterial Agspecific Th17-type T cells decrease in active tuberculosis.…”

Section: Discussionmentioning

confidence: 93%

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Yoshida

Umemura

Yahagi

et al. 2010

The Journal of Immunology

347

261

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Granulomas play an essential role in the sequestration and killing of mycobacteria in the lung; however, the mechanisms of their development and maturation are still not clearly understood. IL-17A is involved in mature granuloma formation in the mycobacteria-infected lung. Therefore, IL-17A gene-knockout (KO) mice fail to develop mature granulomas in the Mycobacterium bovis bacille Calmette-Guérin (BCG)-infected lung. This study analyzed the mechanism of IL-17A–dependent mature granuloma formation in the mycobacteria-infected lung. The IL-17A KO mice showed a normal level of nascent granuloma formation on day 14 but failed to develop mature granulomas on day 28 after the BCG infection in the lung. The observation implies that IL-17A is required for the maturation of granuloma from the nascent to mature stage. TCR γδ T cells expressing TCR Vγ4 or Vγ6 were identified as the major IL-17A–producing cells that resided in the BCG-induced lung granuloma. The adoptive transfer of the IL-17A–producing TCR γδ T cells reconstituted granuloma formation in the IL-17A KO mice. The expression of ICAM-1 and LFA-1, which are adhesion molecules important in granuloma formation, decreased in the lung of the BCG-infected IL-17A KO mice, and their expression was induced on BCG-infected macrophages in coculture with IL-17A–producing TCR γδ T cells. Furthermore, IL-17A KO mice showed not only an impaired mature granuloma formation, but also an impaired protective response to virulent Mycobacterium tuberculosis. Therefore, IL-17A produced by TCR γδ T cells plays a critical role in the prevention of M. tuberculosis infection through the induction of mature granuloma formation.

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“…Interestingly, this profile was mycobacterialantigens-specific as stimulation with PHA (mitogen) showed no differences between the groups. A higher proportion of single-TNF-α producing CD4 + and CD8 + T cells in active TB patients compared with latent TB infected (LTBI) or treated patients is well documented, with high single-TNF-α production associated with active TB disease [18][19][20][21][22][23][24][25]. TNF-α controls MTBC infection progression to disease as evidenced by the increase incidence of active TB in patients treated with anti-TNF-α [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Following flow cytometry analysis, three patients had poor quality data at baseline; therefore, data from 18 Maf-and 27 Mtb-infected patients were examined before treatment. Thirty-three patients were successfully followed up after treatment (14)(15)(16)(17)(18)(19); all were sputum acid-fast bacilli (AFB) smearnegative after 6 months of treatment. …”

mentioning

confidence: 99%

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

et al. 2014

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In The Gambia, Mycobacterium tuberculosis (Mtb) and Mycobacterium africanum (Maf) are major causes of tuberculosis (TB). Maf is more likely to cause TB in immune suppressed individuals, implying differences in virulence. Despite this, few studies have assessed the underlying immunity to the two pathogens in human. In this study, we analyzed T-cell responses from 19 Maf-and 29 Mtb-infected HIV-negative patients before and after TB chemotherapy following overnight stimulation of whole blood with TB-specific antigens. Before treatment, percentages of early secreted antigenic target-6(ESAT-6)/culture filtrate protein-10(CFP-10) and purified protein derivative-specific single-TNF-α-producing CD4 + and CD8 + T cells were significantly higher while single-IL-2-producing T cells were significantly lower in Maf-compared with Mtb-infected patients. Purified protein derivativespecific polyfunctional CD4 + T cells frequencies were significantly higher before than after treatment, but there was no difference between the groups at both time points. Furthermore, the proportion of CD3 + CD11b + T cells was similar in both groups pretreatment, but was significantly lower with higher TNF-α, IL-2, and IFN-γ production in Mtbcompared with that of Maf-infected patients posttreatment. Our data provide evidence of differences in T-cell responses to two mycobacterial strains with differing virulence, providing some insight into TB pathogenesis with different Mtb strains that could be prospectively explored as biomarkers for TB protection or susceptibility. Keywords: Cytokines r Mycobacterium africanum r Mycobacterium tuberculosis r T cells r TuberculosisAdditional supporting information may be found in the online version of this article at the publisher's web-site 1388 Leopold D. Tientcheu et al. Eur. J. Immunol. 2014. 44: 1387-1398 TB is caused by two distinct strains Mycobacterium africanum (Maf) and Mycobacterium tuberculosis (Mtb), with Maf causing up to half of all TB [2]. In The Gambia, TB patients infected with Maf West African type 2 are more likely to be older, HIV coinfected, and/or severely malnourished [3]. In addition, their exposed household contacts have a slower rate of progression to active disease compared with their Mtb-exposed counterparts [4], suggesting that Maf might be the less virulent of the two prevalent strains [5,6]. The heterogeneity in chest x-rays, bacillary load in sputum and clinical symptoms, likely reflects the variation in host immune response to the invading pathogen, and/or the differences between the lineages within the MTBC. For instance, Maf has slower growth in culture medium compared with Mtb [6,7], which may influence progression to active disease [4].The recently published genome of Maf reveals a high content of pseudogenes and the presence of a unique sequence -the region of difference 900 "RD900" that has been deleted evolutionarily from Mtb and M. bovis strains [8]. Many studies have concentrated on the pathogen strain differences in various geographical locations, with only a few anal...

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Pattern and diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease

Cited by 192 publications

References 27 publications

Polyfunctional T cells in human tuberculosis

Polyfunctional T cells in human tuberculosis

Essential Role of IL-17A in the Formation of a Mycobacterial Infection-Induced Granuloma in the Lung

Differences in T‐cell responses between Mycobacterium tuberculosis and Mycobacterium africanum‐infected patients

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