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<p>Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in <i>Mtb</i> antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve <i>Mtb</i> infection detection among exposed household contacts (HHCs) and are associated with index case <i>Mtb</i> aerosolization (i.e., cough aerosol culture positive for Mtb growth, CAC+) and HIV co-infection. We enrolled individuals with PTB and their HHCs in a longitudinal study in Nairobi, Kenya. We measured TNF and IL-2 in HHCs from QuantiFERON-TB Plus TB1 tube supernatants. An additional 9.2% (25) HHCs beyond the 58.6% (129) with an IFN-γ response demonstrated an antigen-specific increase in IL-2 and TNF. HHCs of CAC + participants were more likely to have positive IL-2 (84.6% vs. 53.8%, <i>p</i> = 0.02) and IFN-γ (88.0% vs. 54.9%, <i>p</i> = 0.01), but not TNF responses, compared to CAC-negative individuals. While HIV co-infection in the index was negatively associated with IFN-γ responses in HHCs (35.7% vs. 62.3%, <i>p</i> = 0.03), IL-2 and TNF responses did not differ. Antigen-specific ESAT6/CFP10 IL-2 and TNF may increase rates of <i>Mtb</i> infection detection and provide insights into <i>Mtb</i> transmission and pathogenesis.</p>

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Association of Mycobacterium tuberculosis aerosolization and HIV coinfection in the index case with T cell responses in household contacts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月2日

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  • Lilian N. Njagi,
  • Videlis Nduba,
  • Wilfred Bundi Murithi,
  • Zipporah Mwongera,
  • Kennadi Cook,
  • Jerphason Mecha,
  • Robi Chacha,
  • Kevin P. Fennelly,
  • David J. Horne,
  • Thomas R. Hawn

摘要

Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i.e., cough aerosol culture positive for Mtb growth, CAC+) and HIV co-infection. We enrolled individuals with PTB and their HHCs in a longitudinal study in Nairobi, Kenya. We measured TNF and IL-2 in HHCs from QuantiFERON-TB Plus TB1 tube supernatants. An additional 9.2% (25) HHCs beyond the 58.6% (129) with an IFN-γ response demonstrated an antigen-specific increase in IL-2 and TNF. HHCs of CAC + participants were more likely to have positive IL-2 (84.6% vs. 53.8%, p = 0.02) and IFN-γ (88.0% vs. 54.9%, p = 0.01), but not TNF responses, compared to CAC-negative individuals. While HIV co-infection in the index was negatively associated with IFN-γ responses in HHCs (35.7% vs. 62.3%, p = 0.03), IL-2 and TNF responses did not differ. Antigen-specific ESAT6/CFP10 IL-2 and TNF may increase rates of Mtb infection detection and provide insights into Mtb transmission and pathogenesis.