BCG vaccination prevents reactivation of latent lymphatic murine tuberculosis independently of CD4+ T cells

Sathkumara, Harindra D., Pai, Saparna, de Jesús Aceves-Sánchez, Michel, Ketheesan, Natkunam, Flores-Valdez, Mario Alberto, and Kupz, Andreas (2019) BCG vaccination prevents reactivation of latent lymphatic murine tuberculosis independently of CD4+ T cells. Frontiers in Immunology, 10. 532.

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Tuberculosis (TB) is a major global public health problem causing significant mortality and morbidity. In addition to ~10.4 million cases of active TB annually, it is estimated that about two billion people are latently infected with Mycobacterium tuberculosis (Mtb), the causative agent of TB. Reactivation of latent Mtb infection is the leading cause of death in patients with immunodeficiency virus (HIV) infection. The low efficiency of the only licensed anti-TB vaccine, Bacille Calmette–Guérin (BCG) to reduce pulmonary TB in adults contributes to this problem. Here we investigated if vaccination with conventional BCG or the genetically modified experimental BCGΔBCG1419c strain can prevent reactivation of latent lymphatic TB in a mouse model of induced reactivation, following the depletion of CD4+ T cells, as it occurs in HIV+ individuals. Vaccination with conventional BCG or BCGΔBCG1419c prevented reactivation of Mtb from the infected lymph node and the systemic spread of Mtb to spleen and lung. Prevention of reactivation was independent of vaccination route and was accompanied by reduced levels of circulating inflammatory cytokines and the absence of lung pathology. Our results demonstrate that vaccine-induced CD4+ T cells are not essential to prevent reactivation of latent lymphatic murine TB, and highlight the need to better understand how non-CD4+ immune cell populations participate in protective immune responses to control latent TB.

Item ID: 59051
Item Type: Article (Research - C1)
ISSN: 1664-3224
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Copyright Information: Copyright © 2019 Sathkumara, Pai, Aceves-Sánchez, Ketheesan, Flores-Valdez and Kupz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0).
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A version of this publication was included as Chapter 3 of the following PhD thesis: Sathkumara, Harindra Darshana (2020) Mechanisms driving tuberculosis susceptibility and vaccine efficacy in HIV/AIDS and type 2 diabetes. PhD thesis, James Cook University, which is available Open Access in ResearchOnline@JCU. Please see the Related URLs for access.

Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC APP1052764, NHMRC APP1140709, NHMRC APP1120808
Date Deposited: 02 Aug 2019 04:42
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320499 Immunology not elsewhere classified @ 33%
31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310799 Microbiology not elsewhere classified @ 34%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320299 Clinical sciences not elsewhere classified @ 33%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 50%
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