Variability in Tuberculosis Granuloma T Cell Responses Exists, but a Balance of Pro- and Anti-inflammatory Cytokines Is Associated with Sterilization


The characteristic feature of Mycobacterium tuberculosis (Mtb) infection is the formation of lesions, which are organized structures of immune cells in the lungs called granulomas, which contain the bacteria. When the granuloma functions effectively, it can kill the bacteria. T cells (a type of immune cell, also present in granulomas) are known to play an important role in control of tuberculosis. However, functions of T cells at individual granuloma levels are unknown. Here, we studied the functional characteristics of T cells, which are defined by the production of chemical messengers (cytokines) at the granuloma level in a non-human primate model. We compared the relationship between cytokine response and the number of bacteria (Mtb) in each granuloma. Each granuloma was found to be unique, suggesting different types exist within an animal. Only a small proportion of T cells produced any cytokine, but different types of cytokines were observed within each granuloma. A balance between different types of cytokine was associated with more killing of bacteria in granulomas. Understanding how to improve the T cell responses to obtain killing of bacteria in the granuloma will be important for vaccine development.


Vyšlo v časopise: Variability in Tuberculosis Granuloma T Cell Responses Exists, but a Balance of Pro- and Anti-inflammatory Cytokines Is Associated with Sterilization. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004603
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004603

Souhrn

The characteristic feature of Mycobacterium tuberculosis (Mtb) infection is the formation of lesions, which are organized structures of immune cells in the lungs called granulomas, which contain the bacteria. When the granuloma functions effectively, it can kill the bacteria. T cells (a type of immune cell, also present in granulomas) are known to play an important role in control of tuberculosis. However, functions of T cells at individual granuloma levels are unknown. Here, we studied the functional characteristics of T cells, which are defined by the production of chemical messengers (cytokines) at the granuloma level in a non-human primate model. We compared the relationship between cytokine response and the number of bacteria (Mtb) in each granuloma. Each granuloma was found to be unique, suggesting different types exist within an animal. Only a small proportion of T cells produced any cytokine, but different types of cytokines were observed within each granuloma. A balance between different types of cytokine was associated with more killing of bacteria in granulomas. Understanding how to improve the T cell responses to obtain killing of bacteria in the granuloma will be important for vaccine development.


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