NK cells contribute to the early clearance of HSV-1 from the lung but cannot control replication in the central nervous system following intranasal infection.
While infection of the respiratory tract with herpes simplex virus type 1 (HSV-1) can have severe clinical complications, little is known of the immune mechanisms that control both the replication and spread of HSV-1 in this site. To better understand the contribution of innate immunity and in particular natural killer (NK) cells to the control of infection at this site, we have utilized a mouse model of intranasal HSV-1 infection. NK cell numbers increased in the lung following intranasal infection and they produced IFN-gamma and acquired an enhanced cytotoxic capacity. While depletion of NK cells resulted in increased HSV-1 titres in the lung, the time taken to clear the virus was unaffected. Interestingly, HSV-1 was also effectively cleared from the lungs of RAG-1-/- mice that lack both B and T cells. However, RAG-1-/- mice could not control the spread of virus to the central nervous system and its subsequent replication in the brain. Together, these data demonstrate that NK cells are recruited, activated and contribute to early protection of the lung during acute HSV-1 infection of the respiratory tract, but in the absence of adaptive immunity are unable to control the replication and spread of virus in the nervous system.
Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia. preading@unimelb.edu.au
Patrick C
PC
Reading
Paul G
PG
Whitney
Daniel P
DP
Barr
Mark J
MJ
Smyth
Andrew G
AG
Brooks
D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000821:virology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014779:Virus Replication / Q000276:immunology*
D007371:Interferon-gamma