NLRC3 in septic immunosuppression: Variation in expression and mechanisms of mediating immune cell dysfunction (Review).

Sepsis is a life-threatening disease caused by a dysregulated host immune response to infection. In the acute phase of sepsis, patients tend to experience a hyperinflammatory state; however, in addition to facilitating the elimination of invading pathogens, this severe hyperinflammatory response can also lead to damage to the host. Thus, to maintain immune system homeostasis, counterregulatory immune responses, referred to as compensatory anti-inflammatory responses (CARs), are initiated. However, in the context of sepsis, the stabilization of the immune system cannot be sustained and protracted CARs can lead to an immunosuppressive state, which makes septic patients highly susceptible to secondary infection and high mortality. Various studies have indicated that the expression of NOD-like receptor (NLR) with a caspase activation and recruitment domain 3 (NLRC3), a member of the NLR family, tends to decrease several hours to days after the onset of infection but afterward increases over time and can mediate the dysfunction of immune effector cells in numerous ways, playing a crucial role in the development of septic immunosuppression. Therefore, this review summarized the expression variation of NLRC3 and the mechanisms through which it mediates immune cell dysfunction in different phases of sepsis, seeking to inspire future immune therapy for modulating septic host immune balance and reversing the immunosuppressive state, with a focus on NLRC3 as a target.