Daily Sepsis Research Analysis

Neutrophil migration to bacterial infection sites is key for host defense. Host ribosomal protein SA (RPSA) has been recently reported to regulate the anti-infection immunity of immune cells; however, its role in neutrophil migration remains unclear. Here, using myeloid-specific Rpsa-deficient mice, we found that RPSA deletion inhibited neutrophil infiltration and markedly exacerbated Streptococcus suis serotype 2 infection. Adoptive cell transfer and neutrophil depletion assays identified RPSA as vital for the anti-infective function of neutrophils. Mechanistically, RPSA deficiency induced the overexpression of olfactomedin 4 (OLFM4), which in turn inhibited the activation of the RhoA/ROCK1/pMLC2 signaling pathway, reduced MYH9 expression, and caused aberrant MYH9 translocation from the uropod to the cytosol in migrating neutrophils. Ultimately, this disrupted cytoskeletal polarization and uropod extension, thereby abrogating migratory function. Clinically, septic patients' neutrophils exhibited reduced RPSA and elevated OLFM4 expression, a phenotype that correlated with a marked impairment of migratory capacity. Therapeutic targeting of the RPSA-OLFM4 axis restored neutrophil migration and improved disease outcomes in both S. suis 2-infected and septic mice. Thus, our findings demonstrate that RPSA promotes neutrophil migration via downregulating OLFM4 to counter bacterial infection, and establish the RPSA-OLFM4 axis as a critical immune migratory checkpoint in host antibacterial immunity.

Inflammation is a defining feature of sepsis and a major determinant of disease progression, organ dysfunction, and mortality. Excessive inflammatory responses during the early stage not only cause direct tissue injury but also shape subsequent immune suppression. Macrophages are central orchestrators of this early immune response; however, the molecular regulators that govern macrophage activation in sepsis remain incompletely understood. In this study, integrated bioinformatic analyses of lipopolysaccharide (LPS)-stimulated macrophages combined with experimental validation were performed to identify key regulatory factors and elucidate the underlying mechanisms driving inflammatory responses. An LPS-induced mouse model of sepsis was used to evaluate the therapeutic potential of pharmacological key factor inhibition. In addition, public transcriptomic datasets from sepsis patients were analyzed to assess the clinical relevance of its expression. The results demonstrated that CHD1 was identified as a previously unrecognized regulator of macrophage-driven inflammation in sepsis. CHD1 expression was induced in macrophages following LPS stimulation through the TLR4/MyD88 signaling axis. Mechanistically, CHD1 amplified pro-inflammatory cytokine production by interacting with NF-κB. Early pharmacological inhibition of CHD1 markedly improved survival and alleviated multi-organ injury in septic mice. Furthermore, analysis of clinical transcriptome datasets revealed that elevated blood CHD1 expression in early sepsis was associated with disease severity and poor prognosis. Collectively, this study identifies macrophage-derived CHD1 as a critical driver of inflammation in sepsis by selectively enhancing NF-κB-dependent inflammatory transcription. Targeting CHD1 represents a promising strategy for early intervention in sepsis and may provide both prognostic and therapeutic value.

BACKGROUND: Maternal sepsis and maternal infections (MSMI) are significant causes of maternal mortality in low- and middle-income countries (LMICs). This study, leveraging data from the Global Burden of Disease Study 2023 (GBD 2023), intended to evaluate the trends in the disease burden of MSMI in LMICs from 1990 to 2023, along with its inequality characteristics and future trends. METHODS: Based on the GBD 2023 database, data on the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of MSMI in 129 LMICs from 1990 to 2023 were extracted. Joinpoint regression, decomposition analysis, and health inequality analysis were employed to evaluate changes in disease burden and their driving factors. An autoregressive integrated moving average (ARIMA) model was established to predict trends in disease burden from 2024 to 2035. RESULTS: From 1990 to 2023, the relative burden of MSMI in LMICs generally declined, and the most pronounced decrease was observed in the DALYs rate (estimated annual percentage change (estimated annual percentage change (EAPC) = -3.11, 95% confidence interval (CI): -3.26 to -2.95). However, the absolute burden showed a divergent trend. Specifically, the number of incident cases and prevalent cases increased by 24% and 33%, respectively, while the number of deaths and DALYs decreased by 37% and 39%, respectively. Stratified analysis uncovered that the burden worsened in low-income (gross national income (GNI)-L) countries (with incident cases and prevalent cases rising by 126% and 109%, respectively), whereas decreases were more significant in upper-middle-income (GNI-UM) countries (with deaths and DALYs decreasing by 83% and 81%, respectively). The increased burden in GNI-L countries was primarily driven by population growth, with relative contributions to the incidence burden and prevalence burden of 121.6% and 136.5%, respectively. In addition, widening health inequalities were observed. The concentration indexes for the DALYs rate and mortality rate decreased from -0.392 to -0.594 and from -0.395 to -0.603, respectively. ARIMA projections indicated that while the mortality rate was expected to continue to decline from 2024 to 2035 (with an average annual decrease of -6.4%), the decrease in the incidence rate was projected to be limited (with an average annual decrease of -0.82%). CONCLUSION: Over the past three decades, while the overall burden of MSMI in LMICs has decreased, the control of its absolute burden remains insufficient. GNI-L countries continue to bear a higher burden and experience widening health inequalities. Future prevention and control efforts should not only focus on continuously reducing the overall burden but also prioritize targeted resource allocation for GNI-L countries. Moreover, equity should be integrated into routine monitoring and evaluation systems.