Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection

Oct 5, 2011The Journal of experimental medicine

Interferon-gamma controls neutrophils to reduce lung inflammation during tuberculosis infection

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Abstract

IFN-γ plays a crucial role in preventing harmful inflammation during tuberculosis infection.

Memory CD4(+) T cells lacking IFN-γ maintain their ability to combat bacterial replication but cannot control inflammation.
IFN-γ suppresses the production of IL-17 by CD4(+) T cells, which is involved in recruiting neutrophils.
The presence of IFN-γ limits the accumulation of harmful neutrophils in the lungs infected with tuberculosis.
Neutrophil buildup can be harmful to the host and may signal a failure of Th1 immunity or a lack of IFN-γ responsiveness.
These findings highlight an anti-inflammatory function of IFN-γ that is essential for protecting against tuberculosis.

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Resistance to Mycobacterium tuberculosis requires the host to restrict bacterial replication while preventing an over-exuberant inflammatory response. Interferon (IFN) γ is crucial for activating macrophages and also regulates tissue inflammation. We dissociate these two functions and show that IFN-γ(-/-) memory CD4(+) T cells retain their antimicrobial activity but are unable to suppress inflammation. IFN-γ inhibits CD4(+) T cell production of IL-17, which regulates neutrophil recruitment. In addition, IFN-γ directly inhibits pathogenic neutrophil accumulation in the infected lung and impairs neutrophil survival. Regulation of neutrophils is important because their accumulation is detrimental to the host. We suggest that neutrophilia during tuberculosis indicates failed Th1 immunity or loss of IFN-γ responsiveness. These results establish an important antiinflammatory role for IFN-γ in host protection against tuberculosis.

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Abstract

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