The state of latency in microbial pathogenesis
Liise-anne Pirofski, Arturo Casadevall
Liise-anne Pirofski, Arturo Casadevall
Published August 17, 2020
Citation Information: J Clin Invest. 2020;130(9):4525-4531. https://doi.org/10.1172/JCI136221.
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The state of latency in microbial pathogenesis

Abstract

The state of latency occurs when a microbe’s persistence in a host produces host damage without perturbing homeostasis sufficiently to cause clinical symptoms or disease. The mechanisms contributing to latency are diverse and depend on the nature of both the microbe and the host. Latency has advantages for both host and microbe. The host avoids progressive damage caused by interaction with the microbe that may translate into disease, and the microbe secures a stable niche in which to survive. Latency is clinically important because some latent microbes can be transmitted to other hosts, and it is associated with a risk for recrudescent microbial growth and development of disease. In addition, it can predispose the host to other diseases, such as malignancies. Hence, latency is a temporally unstable state with an eventual outcome that mainly depends on host immunity. Latency is an integral part of the pathogenic strategies of microbes that require human (and/or mammalian) hosts, including herpesviruses, retroviruses, Mycobacterium tuberculosis, and Toxoplasma gondii. However, latency is also an outcome of infection with environmental organisms such as Cryptococcus neoformans, which require no host in their replicative cycles. For most microbes that achieve latency, there is a need for a better understanding and more investigation of host and microbial mechanisms that result in this state.

Authors

Liise-anne Pirofski, Arturo Casadevall

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Figure 1

Microbial latency in the context of the DRF.

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Microbial latency in the context of the DRF. The DRF views latency as an...
The DRF views latency as an outcome of host-microbe interaction. In this state, the host is asymptomatic because the degree of damage resulting from host-microbe interaction is not sufficient to perturb homeostasis. All forms of latency involve some damage to the host at the cellular and/or tissue level. We posit that reactivation can occur at either horn of the parabola. Reactivation of latent microbes such as M. tuberculosis, C. neoformans, T. gondii, and HSV is often associated with conditions that impair the immune response. Reactivation is manifested clinically by recurrence of disease in the setting of immune suppression or weak immunity (the left side of the parabola). However, strong immune responses that result in dysregulation of inflammation may also affect the host-microbe relationship and lead to reactivation, e.g., in tuberculosis and cryptococcosis. This is manifested clinically by a recurrence of disease. For example, reactivation of tuberculosis with caseous necrosis that does not eradicate mycobacteria stems from a strong immune response, and tuberculosis-associated and cryptococcosis-associated immune reconstitution inflammatory syndromes (IRIS) result in immune damage in the setting of an augmented immune response to microbial antigens. Although some of these antigens are likely to be material released from dead microbes, ability of both tuberculosis and cryptococcosis to recur after treatment means that viable cells remain in tissue. HIV (left side of the parabola) is marked with an asterisk because this organism continues to damage the immune system during its latent quiescent state and thus differs from the others as creating its own conditions for the progression to AIDS. HIV (right side of the parabola) is a strategic target for reactivation to reduce the reservoir of latently infected CD4+ T cells, e.g., with chimeric antigen receptor (CAR) T cells (55).