TY - JOUR
T1 - Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation
AU - McGowan, Erin N.S.
AU - Wong, Osanna
AU - Jones, Eleanor
AU - Nguyen, Julie
AU - Wee, Janet
AU - Demaria, Maria C.
AU - Deliyanti, Devy
AU - Johnson, Chad J.
AU - Hickey, Michael J.
AU - McConville, Malcolm J.
AU - Wilkinson-Berka, Jennifer L.
AU - Wright, Mark D.
AU - Binger, Katrina J.
N1 - Funding Information:
This work was supported by the National Health and Medical Research Council (NHMRC), and internal funding from the University of Melbourne, Monash University and La Trobe University. The authors would like to acknowledge the Melbourne Advanced Microscopy Facility (University of Melbourne, Australia) and the La Trobe Bioimaging Facility (La Trobe University, Australia). ENSM, OW, EJ, JN, JW, MCD, DD, CJJ, MJH, and KJB – conducted experiments and analyzed data; MJH, MJM, JLWB, MDW, and KJB – acquired funding, conceived study, supervised project; MDW and KJB – wrote and edited manuscript. All authors saw and approved a final version of the manuscript before submission. The authors declare no competing interests.
Funding Information:
This work was supported by the National Health and Medical Research Council (NHMRC), and internal funding from the University of Melbourne , Monash University and La Trobe University . The authors would like to acknowledge the Melbourne Advanced Microscopy Facility (University of Melbourne, Australia) and the La Trobe Bioimaging Facility (La Trobe University, Australia).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/7/15
Y1 - 2022/7/15
N2 - 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.
AB - 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.
KW - Biological sciences
KW - Immune system
KW - Immunology
UR - http://www.scopus.com/inward/record.url?scp=85132361997&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.104520
DO - 10.1016/j.isci.2022.104520
M3 - Article
C2 - 35754722
AN - SCOPUS:85132361997
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 7
M1 - 104520
ER -