Cabrera, S. | Search bioRxiv

bioRxiv2026

Autophagy impairment by ATG4B deficiency reduces experimental hypersensitivity pneumonitis severity

Autophagy has been implicated in several lung diseases, either protecting tissues or driving pathology. Hypersensitivity pneumonitis (HP) is a complex inflammatory lung disease, and autophagy is heavily involved in regulating inflammation. The role of autophagy in HP remains unclear. The aim of our study was to understand the role of autophagy in HP pathogenesis. GFP-LC3 transgenic mice were exposed intranasally to Saccharopolyspora rectivirgula (SR) to induce HP and follow autophagy activation in the lung. Then, we take advantage of our Atg4b-deficient mouse model to assess how autophagy disruption impacts lung inflammation in response to SR antigen challenge. Increased autophagy activation was observed in epithelial and inflammatory cells after SR antigen exposure in GFP-LC3 transgenic lungs. GFP-LC3 puncta colocalized with ATG4B and ATG5 in epithelial and inflammatory cells after antigen exposure. Autophagy impairment limits the inflammatory response after SR antigen exposure in the lungs from the Atg4b-deficient mice when compared to WT mice. To evaluate whether lipopolysaccharide (LPS) exacerbates the inflammatory response in the Atg4b-deficient, a SR+LPS combined treatment was developed and we discovered that LPS aggravates the SR-induced HP in WT but not in Atg4b-deficient mice. Reduced HP severity in Atg4b-deficient mice was associated with decreased expression of NFkB, CCL1, CCL25, CXCL1, TNFR1, IL-13, and IL-17A, diminished CD4+ T cell recruitment and expansion, reduced M2-like macrophages, and decreased granuloma and iBALT development. Our findings highlight autophagy as a critical driver in HP pathogenesis and as a potetial target for novel theraphy development.

immunology↗

bioRxiv2024

Mechanistic pathways of tick exposure risk in native and invaded plant communities

Plant invasions may alter disease vector abundance by several mechanistic pathways, including modifying microclimates that influence vector survival or changing habitats to influence host use. Here, we used a field experiment and observational data to evaluate multiple mechanistic pathways (tick survival and host abundance) by which plant invasions may alter vector-borne disease risk using the common disease vector lone star tick (Amblyomma americanum), its preeminent host white-tailed deer (Odocoileus virginianus), and the widespread invasive cogongrass (Imperata cylindrica) in the southeastern USA. In the field experiment, ticks survived over 50% longer in areas dominated by the invasive plant compared to those with only native plant species. Invaded areas had lower temperatures and higher relative humidity, yielding a lower vapor pressure deficit (VPD) that likely reduced tick desiccation. The observational study showed similar average tick abundance in native and invaded plant communities and no difference in wildlife host (white-tailed deer) activity between plant communities. However, there was a positive relationship between tick abundance and white-tailed deer activity, but only in native areas. Together, these results suggest that more favorable microclimate conditions resulting in greater tick longevity are the dominant driver of tick abundance in invaded areas, while tick abundance in native-dominated areas may be promoted, at least in part, by white-tailed deer activity. Our results demonstrate that plant invasions can affect multiple, potentially counteracting mechanistic pathways that contribute to tick exposure risk. The complexity of these relationships highlights the need for better understanding of how invasive species and other global change drivers influence disease vectors and, ultimately, disease transmission.

ecology↗