CD5L, a protein expressed and secreted mainly by macrophages, is emerging as a critical immune effector. In addition to its well-defined function as an anti-apoptotic protein, research over the last decade has uncovered additional roles that range from pattern recognition to autophagy, cell polarization, and the regulation of lipid metabolism. By modulating all these processes, CD5L plays a key role in highly prevalent diseases that develop by either acute or chronic inflammation, including several infectious, metabolic, and autoimmune conditions. In this review, we summarize the current knowledge of CD5L and focus on the relevance of this protein during infection- and sterile-driven inflammatory pathogenesis, highlighting its divergent roles in the modulation of inflammation.

Background Malaria caused by Plasmodium falciparum remains a major global health challenge. Although clinical disease results from asexual blood-stage replication, transmission depends on gametocyte carriage. We characterized the seasonal dynamics of the human infectious reservoir in a seasonal, high-transmission setting in Burkina Faso. Methods In this longitudinal cohort study with cross-sectional surveys, conducted between March, 2019, and March, 2021, we followed 864 individuals of all ages from four villages in the Nanoro health district, Burkina Faso, selected from the health and demographic surveillance system by age group; pregnant women and individuals with underlying disease were excluded. Participants were actively screened for asymptomatic infection three times per year and passively monitored for clinical malaria. P. falciparum infections were detected by light microscopy and quantitative PCR targeting parasite DNA and gametocyte-specific RNA. Primary outcomes were the prevalence of asymptomatic infection and gametocyte carriage across transmission seasons. Findings Clinical and asymptomatic infections both showed marked seasonality, peaking in the high-transmission season (HTS, July-December): 685/881 (77.8%) to 748/814 (91.8%) of clinical cases occurred in this period. Asymptomatic infections were prevalent during both the low-transmission season (LTS; 262/663 [39.5%] to 379/811 [46.7%]) and HTS (324/596 [54.4%] to 345/544 [61.0%]), with a higher proportion of gametocyte carriage during LTS (147/261 [55.1%] to 223/367 [60.8%]); compared to HTS (103/298 [34.7%] to 174/314 [55.1%]). Age was the strongest predictor of both asymptomatic infection and gametocyte carriage; children aged 5-12 years formed the largest, persistent reservoir across seasons. Transmission potential was highest in children younger than 13 years and peaked at during LTS. Interpretation School-aged children represent a key, under-targeted reservoir sustaining malaria transmission across seasons in this high-transmission setting. Targeted interventions delivered during the low-transmission season, alongside existing control measures, could reduce gametocyte carriage and shrink the infectious reservoir before the onset of the HTS.