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.

[img]
Preview
PDF (Published version) - Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview
 
27


Abstract

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
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).
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: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 33%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060599 Microbiology not elsewhere classified @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110399 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%
Downloads: Total: 27
Last 12 Months: 27
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page