» Articles » PMID: 23396944

IL-10 Inhibits Mature Fibrotic Granuloma Formation During Mycobacterium Tuberculosis Infection

Overview
Journal J Immunol
Date 2013 Feb 12
PMID 23396944
Citations 57
Authors
Affiliations
Soon will be listed here.
Abstract

Protective immunity and latent Mycobacterium tuberculosis infection in humans are associated with the formation of mature protective granulomas within the lung. Unfortunately, understanding the importance of such structures has been hindered by the lack of small-animal models that can develop mature granulomas. In this article, we describe for the first time, to our knowledge, the formation of mature, fibrotic M. tuberculosis-containing pulmonary granulomas in a mouse model of IL-10 deficiency (CBA/J IL-10(-/-)). Long-term control of M. tuberculosis infection in the absence of IL-10 was also associated with an early and enhanced capacity for Ag presentation and a significant increase in the generation of multifunctional T cells. Although IL-10 deficiency is known to enhance Th1 immune responses in general, we demonstrate in this study using transient anti-IL-10R treatment that it is the presence of IL-10 in vivo during the first month of M. tuberculosis infection that plays a definitive role in the inhibition of optimum protective immunity that can establish the environment for mature granuloma formation. Although the importance of IL-10 during M. tuberculosis infection has been debated, our data demonstrate that in CBA/J mice, IL-10 plays a significant early inhibitory role in preventing the development of protective immunity associated with containment of M. tuberculosis infection.

Citing Articles

Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.

Gatti D, Tyler A, Mahoney J, Churchill G, Yener B, Koyuncu D PLoS Pathog. 2024; 20(6):e1011915.

PMID: 38861581 PMC: 11195971. DOI: 10.1371/journal.ppat.1011915.


Evaluation of cytokine profiles related to latent antigens using a whole-blood assay in the Philippines.

Yasuda I, Saludar N, Sayo A, Suzuki S, Yokoyama A, Ozeki Y Front Immunol. 2024; 15:1330796.

PMID: 38665909 PMC: 11044679. DOI: 10.3389/fimmu.2024.1330796.


Systems genetics uncover new loci containing functional gene candidates in -infected Diversity Outbred mice.

Gatti D, Tyler A, Mahoney J, Churchill G, Yener B, Koyuncu D bioRxiv. 2024; .

PMID: 38187647 PMC: 10769337. DOI: 10.1101/2023.12.21.572738.


Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4 T Cells in Aging.

Headley C, Gautam S, Olmo-Fontanez A, Garcia-Vilanova A, Dwivedi V, Akhter A Adv Sci (Weinh). 2023; 11(5):e2303664.

PMID: 37990641 PMC: 10837346. DOI: 10.1002/advs.202303664.


Characterisation and development of histopathological lesions in a guinea pig model of infection.

Larenas-Munoz F, Ruedas-Torres I, Hunter L, Bird A, Agullo-Ros I, Winsbury R Front Vet Sci. 2023; 10:1264200.

PMID: 37808110 PMC: 10556493. DOI: 10.3389/fvets.2023.1264200.


References
1.
Selwyn P, Hartel D, Lewis V, Schoenbaum E, Vermund S, Klein R . A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med. 1989; 320(9):545-50. DOI: 10.1056/NEJM198903023200901. View

2.
Pichugin A, Yan B, Sloutsky A, Kobzik L, Kramnik I . Dominant role of the sst1 locus in pathogenesis of necrotizing lung granulomas during chronic tuberculosis infection and reactivation in genetically resistant hosts. Am J Pathol. 2009; 174(6):2190-201. PMC: 2684184. DOI: 10.2353/ajpath.2009.081075. View

3.
Blomgran R, Ernst J . Lung neutrophils facilitate activation of naive antigen-specific CD4+ T cells during Mycobacterium tuberculosis infection. J Immunol. 2011; 186(12):7110-9. PMC: 3376160. DOI: 10.4049/jimmunol.1100001. View

4.
Russell D . Who puts the tubercle in tuberculosis?. Nat Rev Microbiol. 2006; 5(1):39-47. DOI: 10.1038/nrmicro1538. View

5.
Redford P, Murray P, OGarra A . The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol. 2011; 4(3):261-70. DOI: 10.1038/mi.2011.7. View