Cytoskeletal and phagolysosomal failure in macrophage antibacterial immunity: the PRRSV–porcine alveolar macrophage axis as a natural-host model
- 1Department of Clinical Laboratory, The First Affiliated Hospital of Dalian Medical University
- 2Department of Comparative Medicine, Dalian Medical University
- 3Department of Nephrology, The First Affiliated Hospital of Dalian Medical University
Abstract
Viral infection of professional phagocytes can compromise antibacterial immunity because the cellular machinery reshaped for viral replication and immune evasion overlaps with the machinery required for bacterial capture, intracellular killing, and inflammatory signaling. Phagocyte cell biology has defined core cytoskeletal and trafficking nodes, including Rho-family GTPase control of actin assembly, integrin-mediated adhesion, and Rab-dependent phagosome maturation, and shown how bacterial pathogens target these nodes to evade clearance. Here we ask how recently described porcine reproductive and respiratory syndrome virus (PRRSV) lesions in porcine alveolar macrophages (PAMs) fit into this established cell biology. Direct evidence supports reduced phagocytic capture and impaired intracellular bacterial killing in defined systems. In vivo coinfection studies also report worse outcomes. Enhanced association or internalization of selected bacteria has also been reported, with ITGα5 and filamin A upregulation proposed as a candidate explanation. PRRSV further disrupts innate-immune signaling, autophagy–lysosome trafficking, ER–mitochondrial metabolism, and lipid homeostasis. These changes may contribute to antibacterial failure, but bacterial endpoints were not measured in the same experiments. At the tissue level, macrophage attrition and altered bystander states may disrupt cytokine relay, creating a permissive lung environment even when only a minority of PAMs are productively infected. PRRSV is particularly informative because it productively infects a professional phagocyte in the natural host, allowing viral perturbation, macrophage antibacterial function, and bacterial challenge to be examined in one tractable system. Because the candidate nsp5–RhoA trafficking route and the ITGα5/FLNA entry route were reported in different experimental systems, their potential combination defines a testable hypothesis requiring co-validation in the same primary PAM system. We use the PRRSV–PAM axis as a natural-host model to examine how viral infection of professional phagocytes can produce macrophage antibacterial failure, with implications for virus-associated bacterial vulnerability in veterinary and human respiratory disease.
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BibTeX
@article{wang2026cytoskeletal,
title = {{Cytoskeletal and phagolysosomal failure in macrophage antibacterial immunity: the PRRSV–porcine alveolar macrophage axis as a natural-host model}},
author = {Yubo Wang and Yihao Shang and Huiyang Yu and Xintong Li and Ailin Ji and Liang Wang and Jilin Chen and Yu Qi},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1892313},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892313/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cytoskeletal and phagolysosomal failure in macrophage antibacterial immunity: the PRRSV–porcine alveolar macrophage axis as a natural-host model
AU - Yubo Wang
AU - Yihao Shang
AU - Huiyang Yu
AU - Xintong Li
AU - Ailin Ji
AU - Liang Wang
AU - Jilin Chen
AU - Yu Qi
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1892313
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892313/full
AB - Viral infection of professional phagocytes can compromise antibacterial immunity because the cellular machinery reshaped for viral replication and immune evasion overlaps with the machinery required for bacterial capture, intracellular killing, and inflammatory signaling. Phagocyte cell biology has defined core cytoskeletal and trafficking nodes, including Rho-family GTPase control of actin assembly, integrin-mediated adhesion, and Rab-dependent phagosome maturation, and shown how bacterial pathogens target these nodes to evade clearance. Here we ask how recently described porcine reproductive and respiratory syndrome virus (PRRSV) lesions in porcine alveolar macrophages (PAMs) fit into this established cell biology. Direct evidence supports reduced phagocytic capture and impaired intracellular bacterial killing in defined systems. In vivo coinfection studies also report worse outcomes. Enhanced association or internalization of selected bacteria has also been reported, with ITGα5 and filamin A upregulation proposed as a candidate explanation. PRRSV further disrupts innate-immune signaling, autophagy–lysosome trafficking, ER–mitochondrial metabolism, and lipid homeostasis. These changes may contribute to antibacterial failure, but bacterial endpoints were not measured in the same experiments. At the tissue level, macrophage attrition and altered bystander states may disrupt cytokine relay, creating a permissive lung environment even when only a minority of PAMs are productively infected. PRRSV is particularly informative because it productively infects a professional phagocyte in the natural host, allowing viral perturbation, macrophage antibacterial function, and bacterial challenge to be examined in one tractable system. Because the candidate nsp5–RhoA trafficking route and the ITGα5/FLNA entry route were reported in different experimental systems, their potential combination defines a testable hypothesis requiring co-validation in the same primary PAM system. We use the PRRSV–PAM axis as a natural-host model to examine how viral infection of professional phagocytes can produce macrophage antibacterial failure, with implications for virus-associated bacterial vulnerability in veterinary and human respiratory disease.
SN - 1664-3224
ER -