HomeIt is now increasingly understood that host defense strategies against infectious diseases comprise both host resistance and disease tolerance. Host resistance is the ability of the host to prevent invasion or to eliminate the pathogen,69 while disease tolerance is defined as limiting the tissue damage caused by the pathogen and/or the immune response. Since the discovery of M. tuberculosis more than a century ago, great progress has been made in defining mechanisms of host resistance to this respiratory pathogen. By contrast, our understanding of natural immunity in the 90 to 95% of infected individuals who remain disease-free is extremely limited.
The inability of both the innate and adaptive immune system to eliminate the bacteria forces the host to develop a cellular barrier, referred to as a granuloma, around infected cells. Granuloma formation appears to be the point at which host immunity “switches” from resistance to tolerance. Indeed, studies have elegantly demonstrated that intercellular communication is organized in the granuloma such that pro-inflammatory signaling occurs at the core to control M. tuberculosis growth, while anti-inflammatory signaling at the periphery acts to limit tissue damage.70,71Thus, the spatial compartmentalization of pro- and anti-inflammatory signaling is critical in granuloma function to prevent M. tuberculosis dissemination.
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