Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation

Erin N S McGowan; Osanna Wong; Eleanor Jones; Julie Nguyen; Janet Wee; Maria C Demaria; Devy Deliyanti; Chad J Johnson; Michael J Hickey; Malcolm J McConville; Jennifer L Wilkinson-Berka; Mark D Wright; Katrina J Binger

doi:10.1016/j.isci.2022.104520

Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation

iScience. 2022 Jun 3;25(7):104520. doi: 10.1016/j.isci.2022.104520. eCollection 2022 Jul 15.

Authors

Erin N S McGowan¹, Osanna Wong², Eleanor Jones^{2

3}, Julie Nguyen^{2

4}, Janet Wee^{2

4}, Maria C Demaria², Devy Deliyanti⁵, Chad J Johnson⁶, Michael J Hickey⁴, Malcolm J McConville¹, Jennifer L Wilkinson-Berka⁵, Mark D Wright², Katrina J Binger^{1

2

7}

Affiliations

¹ Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3052, Australia.
² Department of Immunology and Pathology, Alfred Research Alliance, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
³ Flow Cytometry and Imaging Facility, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
⁴ Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC 3168, Australia.
⁵ Department of Anatomy and Physiology, School of Biomedical Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.
⁶ Bioimaging Platform, La Trobe University, Bundoora, VIC 3086, Australia.
⁷ Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia.

Abstract

Phagocytes migrate into tissues to combat infection and maintain tissue homeostasis. As dysregulated phagocyte migration and function can lead to inflammation or susceptibility to infection, identifying molecules that control these processes is critical. Here, we show that the tetraspanin CD82 restrains the migration of neutrophils and macrophages into tissues. Cd82 ^-/- phagocytes exhibited excessive migration during in vivo models of peritoneal inflammation, superfusion of CXCL1, retinopathy of prematurity, and infection with the protozoan parasite L. mexicana. However, with the latter, while Cd82 ^-/- macrophages infiltrated infection sites at higher proportions, cutaneous L. mexicana lesions were larger and persisted, indicating a failure to control infection. Analyses of in vitro bone-marrow-derived macrophages showed CD82 deficiency altered cellular morphology, and impaired gene expression and metabolism in response to anti-inflammatory activation. Altogether, this work reveals an important role for CD82 in restraining phagocyte infiltration and mediating their differentiation in response to stimulatory cues.

Keywords: Biological sciences; Immune system; Immunology.