Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis

Abstract

Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 exaggerates multiple organ injury, inflammation, and immune cell imbalance by activating the NF-κB pathway in sepsis

“…Multiple organ dysfunction is one of the hallmarks of sepsis ( Cecconi et al, 2018 ). In patients with sepsis, injuries of the lung, liver, kidney, anticoagulant system, heart, nervous system, etc., are likely to occur, which are closely associated with the mortality risk of sepsis ( Zhou and Liao, 2021 ; Lu et al, 2022 ). Previously, some studies have shown that MALT1 is a potential regulator of organ dysfunction.…”

Immunological and Prognostic Role of Hub Genes Defined Gene Signature in Septic Cardiomyopathy

“…Next, as an inevitable immune response of septic cardiomyopathy, the coexistence of SIRS and CARS would cause immune dysfunction and uncontrolled immune-related injury 7,19 . Therefore, another key goal was to clarify the immune landscapes of septic cardiomyopathy.…”

“…However, with the development of supportive therapy, most patients can survive through SIRS and become more complex immunosuppressive CARS 5,6 . The coexistence and reinforcement of SIRS and CARS inevitably lead to immune-related severe injury, which might be the basis of septic cardiomyopathy 7 .…”

Cytokine Storm—Definition, Causes, and Implications

“…The number of MDSCs increases with age [ 199 ]. They are associated with sustained sepsis-induced immunosuppression by promoting T- and B-cell depletion, functional inhibition of DC and macrophages, and by inhibition of NK cells while promoting Treg [ 192 , 200 ].…”