Soil-transmitted helminth (STH) infections affect over a billion people globally, particularly in regions with poor sanitation. Nippostrongylus brasiliensis (Nb), a murine model for human hookworm, causes acute lung injury during larval migration through pulmonary tissue, triggering a type 2 (Th2) immune response essential for parasite clearance and tissue repair. However, this inflammation must be tightly regulated to avoid fibrosis and ensure proper remodeling. Macrophages are critical in this process, yet the mechanisms by which they mediate lung repair remain unclear. One candidate is Resistin-like molecule alpha (RELMα), a secreted protein from alternatively activated macrophages. RELMα is known to limit inflammation and promote remodeling, but its macrophage-specific role in lung repair during helminth infection is poorly defined. While global knockouts suggest a protective role, they fail to pinpoint responsible cell types. This project uses a Cre-loxP conditional knockout model (LysM Cre+/- RELMαFlox/Flox) to delete RELMα in macrophages. Following subcutaneous Nb infection, lung pathology will be assessed on Day 7 using histological scoring for alveolar destruction, vascular inflammation, airway thickening, and leukocyte infiltration. The study includes mouse genotyping, infections, lung harvest, H&E staining, and pathology scoring. Comparisons with wild-type mice revealed that macrophage-derived RELMα modulates inflammation and supports repair. Identifying macrophage-derived RELMα as a central repair regulator will enhance understanding of innate immune contributions to recovery after parasitic infection. These insights may guide immunotherapy development for helminth-related and broader inflammatory lung diseases.

Background

Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.

Methods

The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.

Results

A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.

Conclusions

There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.

Clinical trials registration

NCT02344290.