Depletion of Gr-1+, but not Ly6G+, immune cells exacerbates virus replication and disease in an intranasal model of herpes simplex virus type 1 infection.
In the absence of a viable 'knockout' mouse, researchers have relied extensively on monoclonal antibody (mAb) RB6-8C5 [anti-granulocyte receptor 1 (Gr-1)] to deplete neutrophils in murine models of inflammation and infection. Using an intranasal model of herpes simplex virus type 1 (HSV-1) infection, we demonstrate that mAb RB6-8C5 also binds to plasmacytoid dendritic cells, F4/80(+) macrophages/monocytes and CD8(+) T cells recovered from the airways of HSV-1-infected mice. In contrast, mAb 1A8 (anti-Ly6G) bound specifically to Ly6G(high) neutrophils. Following intranasal infection of C57BL/6 mice with HSV-1, few Ly6G(high) neutrophils were recruited to the airways and treatment of mice with purified mAb 1A8 induced systemic neutropenia, but did not alter virus replication or disease progression. In contrast, treatment of HSV-1-infected mice with mAb RB6-8C5 led to exacerbated virus replication, disease severity and mortality. These findings highlight the limitations associated with widespread use of antibody-mediated depletion of Gr-1(+) cells to define the role of neutrophils in vivo. Furthermore, we use mAb 1A8 to demonstrate that specific depletion of neutrophils does not modulate disease or alter virus replication following intranasal infection with HSV-1.
Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia.
Magdalena
M
Wojtasiak
Danielle L
DL
Pickett
Michelle D
MD
Tate
Sarah L
SL
Londrigan
Sammy
S
Bedoui
Andrew G
AG
Brooks
Patrick C
PC
Reading
D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006561:Herpes Simplex / Q000209:etiology* / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000276:immunology / Q000821:virology; D009504:Neutrophils / Q000276:immunology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; C503133:Gr-1 protein, mouse; C480309:Ly6G antigen, mouse; D019707:Receptors, Chemokine