Attenuated β2 Integrin Expression in Neutrophils Alters Dendritic Cell Stimulation and T Cell Activation in Old Mice
- 1Department of Dermatology, University Medical Center of the Johannes Gutenberg—University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany
- 2Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany
Abstract
Polymorphonuclear neutrophils (PMNs) are critical for defense against bacterial and fungal pathogens, relying on the β2 integrins LFA-1 and MAC-1 to mediate adhesion, phagocytosis, ROS production, and NETosis. β2 integrins are heterodimeric surface receptors that are composed of a variable α (LFA-1: CD11a, MAC-1: CD11b) and CD18 as the constant β subunit. We have previously shown that in mice, partial PMN-specific CD18 knockdown worsens aspergillosis by impairing PMN function. Given that aging also alters PMN behavior, this study aimed to elucidate whether reduced β2 integrins in PMNs of aged mice affect their interactions with other immune cells. Comparing young (8–12 weeks) and aged (>52 weeks) mice, we observed that PMN-specific CD18 reduction remained stable across age groups, with CD18 expression reduced to approximately 60–70% of WT levels. PMNs from aged CD18Ly6G mice showed reduced phagocytosis of A. fumigatus conidia and increased CD86 expression following stimulation. Regarding extrinsic effects, aging was associated with increased MHC class II expression on splenic myeloid cells and an activated T-cell phenotype. Polyclonal stimulation resulted in increased TNF-α production in cultures of splenocytes derived from aged CD18Ly6G mice, and CD4+ T cells were characterized by reduced induction of Th1- and Th2-associated transcription factors. DCs from aged CD18Ly6G mice showed altered activation and cytokine secretion and induced less antigen-specific CD4+ T-cell proliferation. In addition, CD18-knockdown PMNs of aged mice stimulated dendritic cells (DCs) less effectively than WT PMNs. Thus, partial β2 integrin reduction in PMNs impairs selected PMN effector functions and is associated with altered DC activation and CD4+ T-cell responses during aging.
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BibTeX
@article{hieber2026attenuated,
title = {{Attenuated β2 Integrin Expression in Neutrophils Alters Dendritic Cell Stimulation and T Cell Activation in Old Mice}},
author = {Christoph Hieber and Stephan Grabbe and Matthias Bros},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201852},
url = {https://www.mdpi.com/2073-4409/15/20/1852},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Attenuated β2 Integrin Expression in Neutrophils Alters Dendritic Cell Stimulation and T Cell Activation in Old Mice
AU - Christoph Hieber
AU - Stephan Grabbe
AU - Matthias Bros
PY - 2026
DA - 2026/10/12
JO - Cells
DO - 10.3390/cells15201852
UR - https://www.mdpi.com/2073-4409/15/20/1852
AB - Polymorphonuclear neutrophils (PMNs) are critical for defense against bacterial and fungal pathogens, relying on the β2 integrins LFA-1 and MAC-1 to mediate adhesion, phagocytosis, ROS production, and NETosis. β2 integrins are heterodimeric surface receptors that are composed of a variable α (LFA-1: CD11a, MAC-1: CD11b) and CD18 as the constant β subunit. We have previously shown that in mice, partial PMN-specific CD18 knockdown worsens aspergillosis by impairing PMN function. Given that aging also alters PMN behavior, this study aimed to elucidate whether reduced β2 integrins in PMNs of aged mice affect their interactions with other immune cells. Comparing young (8–12 weeks) and aged (>52 weeks) mice, we observed that PMN-specific CD18 reduction remained stable across age groups, with CD18 expression reduced to approximately 60–70% of WT levels. PMNs from aged CD18Ly6G mice showed reduced phagocytosis of A. fumigatus conidia and increased CD86 expression following stimulation. Regarding extrinsic effects, aging was associated with increased MHC class II expression on splenic myeloid cells and an activated T-cell phenotype. Polyclonal stimulation resulted in increased TNF-α production in cultures of splenocytes derived from aged CD18Ly6G mice, and CD4+ T cells were characterized by reduced induction of Th1- and Th2-associated transcription factors. DCs from aged CD18Ly6G mice showed altered activation and cytokine secretion and induced less antigen-specific CD4+ T-cell proliferation. In addition, CD18-knockdown PMNs of aged mice stimulated dendritic cells (DCs) less effectively than WT PMNs. Thus, partial β2 integrin reduction in PMNs impairs selected PMN effector functions and is associated with altered DC activation and CD4+ T-cell responses during aging.
SN - 2073-4409
ER -