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Immunopathogenesis in HIV-associated pediatric tuberculosis

Abstract

Tuberculosis (TB) is an increasing global emergency in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients, in which host immunity is dysregulated and compromised. However, the pathogenesis and efficacy of therapeutic strategies in HIV-associated TB in developing infants are essentially lacking. Bacillus Calmette-Guerin vaccine, an attenuated live strain of Mycobacterium bovis, is not adequately effective, which confers partial protection against Mycobacterium tuberculosis (Mtb) in infants when administered at birth. However, pediatric HIV infection is most devastating in the disease progression of TB. It remains challenging whether early antiretroviral therapy (ART) could maintain immune development and function, and restore Mtb-specific immune function in HIV-associated TB in children. A better understanding of the immunopathogenesis in HIV-associated pediatric Mtb infection is essential to provide more effective interventions, reducing the risk of morbidity and mortality in HIV-associated Mtb infection in infants.

Impact

  • Children living with HIV are more likely prone to opportunistic infection, predisposing high risk of TB diseases.

  • HIV and Mtb coinfection in infants may synergistically accelerate disease progression.

  • Early ART may probably induce immune reconstitution inflammatory syndrome and TB pathology in HIV/Mtb coinfected infants.

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Fig. 1: Pulmonary granulomas in infant macaques with tuberculosis.

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Acknowledgements

This work was supported by NIH grants R01 HD099857 and R01 AI147372. The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation.

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R.V.B. and R.S.V. assisted with manuscript preparation; H.X. and X.W. wrote the manuscript.

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Correspondence to Xiaolei Wang.

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Xu, H., Blair, R.V., Veazey, R.S. et al. Immunopathogenesis in HIV-associated pediatric tuberculosis. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01393-x

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