Tuberculosis defense


Tuberculosis (TB) is one the most prevalent infectious diseases in the world, but only 10% of infected individuals develop active TB.  One of the most important challenges in TB control is to be able to distinguish between patients with latent TB from those with active TB. During TB infection, macrophage aggregates, known as granulomas, form in the lungs to promote macrophage activation and help control TB infection. The formation of granulomas is associated with latent TB, while an absence of granulomas is a characteristic of active TB infection. Using both human and experimental models of TB infection, Slight et al. evaluated the role of CXCR5+ T cells in immune control. Here they show a section of formalin-fixed, paraffin-embedded lung biopsy from a patient with active TB. The sections were analyzed by immunofluorescence using antibodies specific to CD20 (white), IgD (green), and PCNA (red). Additionally, the section was counterstained with DAPI (DNA, blue). These markers indicate the presence of antibody-generating B cells. Slight and colleagues found that the presence of CXCR5+ T cells in lung granulomas were associated with immune control and play a protective role during TB infection.

Published January 2, 2013, by Jillian Hurst

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CXCR5+ T helper cells mediate protective immunity against tuberculosis
Samantha R. Slight, … , Troy D. Randall, Shabaana A. Khader
Samantha R. Slight, … , Troy D. Randall, Shabaana A. Khader
Published January 2, 2013
Citation Information: J Clin Invest. 2013;123(2):712-726. https://doi.org/10.1172/JCI65728.
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Research Article Immunology

CXCR5+ T helper cells mediate protective immunity against tuberculosis

Abstract

One third of the world’s population is infected with Mycobacterium tuberculosis (Mtb). Although most infected people remain asymptomatic, they have a 10% lifetime risk of developing active tuberculosis (TB). Thus, the current challenge is to identify immune parameters that distinguish individuals with latent TB from those with active TB. Using human and experimental models of Mtb infection, we demonstrated that organized ectopic lymphoid structures containing CXCR5+ T cells were present in Mtb-infected lungs. In addition, we found that in experimental Mtb infection models, the presence of CXCR5+ T cells within ectopic lymphoid structures was associated with immune control. Furthermore, in a mouse model of Mtb infection, we showed that activated CD4+CXCR5+ T cells accumulated in Mtb-infected lungs and produced proinflammatory cytokines. Mice deficient in Cxcr5 had increased susceptibility to TB due to defective T cell localization within the lung parenchyma. We demonstrated that CXCR5 expression in T cells mediated correct T cell localization within TB granulomas, promoted efficient macrophage activation, protected against Mtb infection, and facilitated lymphoid follicle formation. These data demonstrate that CD4+CXCR5+ T cells play a protective role in the immune response against TB and highlight their potential use for future TB vaccine design and therapy.

Authors

Samantha R. Slight, Javier Rangel-Moreno, Radha Gopal, Yinyao Lin, Beth A. Fallert Junecko, Smriti Mehra, Moises Selman, Enrique Becerril-Villanueva, Javier Baquera-Heredia, Lenin Pavon, Deepak Kaushal, Todd A. Reinhart, Troy D. Randall, Shabaana A. Khader

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