TREML4 receptor regulates inflammation and innate immune cell death during polymicrobial sepsis

A resolving role for neutrophil CD11d in facilitating neutrophil survival and macrophage efferocytosis during sepsis?

“…The author also demonstrated that endotoxin challenge can robustly induce the expression of CD11d α D on neutrophils as well as reducing neutrophil necrosis, perhaps serving as a compensatory coping mechanism upon septic insult. Consistent with this finding, a recent study independently reported that neutrophils with enhanced survival due to Treml4 deletion contribute to alleviated multiorgan damage during both the acute and chronic phases of experimental sepsis 8 …”

Inflammation and Cell Death of the Innate and Adaptive Immune System during Sepsis

“…Under steady-state conditions, neutrophils are short-lived with a turnover rate of 6-8 h in the circulation [58]. However, during sepsis, mature neutrophils become apoptotic, leading to an expansion of immature neutrophils owing to a delayed apoptotic response (Figure 1) [7]. The persistence of dysregulated immature neutrophils leads to extensive tissue damage as they have increased adhesive properties, allowing them to readily invade tissue and execute damaging functions such as oxidative burst [59].…”

“…The persistence of dysregulated immature neutrophils leads to extensive tissue damage as they have increased adhesive properties, allowing them to readily invade tissue and execute damaging functions such as oxidative burst [59]. Studies have shown that during sepsis, surviving impaired neutrophils persist due to the downregulation of pro-apoptotic proteins, such as Bim and caspases, with concurred upregulation of pro-survival proteins such as BCL-xL [7,60]. Similar studies in mice have also revealed that death of mature neutrophils, during sepsis, is mediated by triggering receptor expressed in myeloid like-4 (Treml4), leading to the prevalence of dysfunctional neutrophils and reduced survival of mice following secondary infection [7].…”

“…Studies have shown that during sepsis, surviving impaired neutrophils persist due to the downregulation of pro-apoptotic proteins, such as Bim and caspases, with concurred upregulation of pro-survival proteins such as BCL-xL [7,60]. Similar studies in mice have also revealed that death of mature neutrophils, during sepsis, is mediated by triggering receptor expressed in myeloid like-4 (Treml4), leading to the prevalence of dysfunctional neutrophils and reduced survival of mice following secondary infection [7]. These findings highlight the importance of neutrophils during sepsis and how their dysregulation negatively impacts survival outcome.…”

“…Here, the immune system exhibits exhaustion and death of cells from both lymphoid and myeloid lineage, leaving patients immunocompromised [6]. The mass depletion of immune cells leaves patients vulnerable to secondary infection, typically caused by nosocomial opportunistic pathogens such as Acinetobacter baumannii (22.2% of cases) Pseudomonas aeruginosa (10.3% of cases), Candida albicans (candidiasis; 8.5% of cases) and viruses (>1% of cases) [7][8][9][10][11][12]. Secondary infections are typically acquired 48 h proceeding the initial infection, suggesting that immune paralysis peaks during this time, however this varies between cases and is dependent on many factors, i.e., patient comorbidities [13].…”