bims-nocaut 2026-05-03 papers

Issue of 2026–05–03
three papers selected by
Quentin Frenger, University of Strasbourg

Microbiol Immunol. 2026 Apr 29.

LC3-Associated Phagocytosis in Hepatitis C Virus-Induced Fibrosis.

Nermine Magdi Riad, Zainab Wafik Masoud, Yasmine Gaber, Rabab El Hawary, Ayman Yosry, Hend H Tamim, Naglaa Ali Zayed, Mariam Onsy F Hanna.

During LC3-associated phagocytosis (LAP), a non-canonical form of autophagy, LC3 is recruited to pathogen and apoptotic cells containing phagosomes, where the phagocytosed cargo is degraded. Given the importance of LAP in host defense and the role of phagocytic cells in liver inflammation and fibrosis, this study assessed LAP in peripheral blood neutrophils and monocytes from patients with variable degrees of liver fibrosis and cirrhosis secondary to viral hepatitis C infection. LAP was quantified by flow cytometry using labeled zymosan as a stimulus to engage LAP and LC3 antibodies to detect LC3 recruitment. LAP engagement was evaluated as the integrated mean fluorescence intensity of LC3 in zymosan-positive cells. LAP was enhanced in patients with mild to moderate liver fibrosis (stages F1-F2) compared with patients with no fibrosis (F0) and severe fibrosis or cirrhosis (stages F3-F4). Furthermore, LAP in both neutrophils and monocytes correlated with the stage of fibrosis from F0 to F2, indicating that as the process of fibrosis progressed in the early stages, LAP activity increased. No differences in LAP were observed between treatment-naïve and those who received direct acting antiviral therapy and achieved sustained virologic response (SVR), suggesting that the process of fibrosis had a more significant impact on LAP, rather than the presence or absence of HCV infection. In conclusion, LAP is enhanced in circulating phagocytes during early stages of HCV-related fibrosis but declines in advanced disease, independent of treatment status and SVR.

Keywords: LC3‐associated phagocytosis; hepatitis C virus; liver cirrhosis; liver fibrosis; monocytes; neutrophils

DOI: https://doi.org/10.1111/1348-0421.70058

J Immunol Res. 2026 ;2026(1): e5542735

Aspergillus fumigatus Gliotoxin Inhibits LC3-Associated Phagocytosis in Macrophages in a Calcium-Dependent Manner.

Yuqing Sun, Fangyan Chen, Ling Zhang, Caopei Zheng, Yu Wang, Yulin Zhang, Li Han.

As a pivotal secondary metabolite of Aspergillus fumigatus, gliotoxin (GT) has many toxicological effects on mammalian cells; however, its function on LC3-associated phagocytosis (LAP) induced by A. fumigatus in macrophages is poorly understood. Here, it was found that pretreatment of macrophages with GT can significantly attenuate the conversion of LC3-II. In parallel, the expression of Rubicon, the putative indicator of LAP in macrophages, was dampened in a similar trend. Loss of ability to produce GT made the conidia of gliPΔ mutant of A. fumigatus induce more LC3-II conversion in THP1 cells, which could be inhibited by exogenous GT. Comparative transcriptomic analysis showed that GT can promote the expression of MAPK10, and the calcium-release regulatory pathway was enriched between the differentially expressed genes. Further, GT promotes the release of ROS at a concentration of 50 ng/mL, and inhibition by GT on LC3-II production in macrophages during A. fumigatus infection could be restored by pretreatment with calcium inhibitors but not affected by the inhibitors for JNK and siRNA for MAKP10. Collectively, our data demonstrated that GT exerts an inhibitory effect on LC3-associated phagocytosis in macrophages via a calcium-dependent mechanism, and MAPK10 exists downstream of LAP.

Keywords: Aspergillus fumigatus; LC3-associated phagocytosis; MAPK10; calcium; gliotoxin

DOI: https://doi.org/10.1155/jimr/5542735

Proc Natl Acad Sci U S A. 2026 May 05. 123(18): e2508391123

ATG9A-mediated plasma membrane repair is linked to Vps13A and regulated by glycosylation.

Natali H Muskat, Inbar Nevo-Yassaf, Madhuri Chaurasia, Shani Reiss, Inna Goliand, Meital Kupervaser, Yoseph Addadi, Yishai Levin, Milana Fraiberg, Zvulun Elazar.

Biological membranes provide a resilient framework for cellular structure and stability. Disrupting its integrity may result in irreparable damage, altering cellular homeostasis and ultimately leading to cell death. ATG9A, a transmembrane protein, has recently been implicated in plasma membrane repair. However, its role in the process and the mechanism by which it is targeted to the plasma membrane upon damage are unclear. We show here that glycosylation of ATG9A is essential for its membrane repair activity. This has been corroborated by using different mutant cells that are defective in their ability to process proteoglycan in the Golgi complex. Specifically, sialylation of the sugar moiety appears vital for plasma membrane repair activity. Additionally, we provide evidence indicating that ATG9A is targeted to the plasma membrane through interaction with the endosomal sorting complex required for transport complex. Finally, we found that ATG9A lipid scramblase activity and the lipid transfer protein VPS13A are needed for efficient membrane repair.

Keywords: ATG9A; ESCRT-comples; Plasma membrane repair; VPS13A; glycosylation

DOI: https://doi.org/10.1073/pnas.2508391123