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

Abstract

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-c 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.

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

“…Neutrophils comprised a small proportion of inflammatory leukocytes recruited to the airways following HSV-1 infection, consistent with our previous findings that activated NK cells and CD8 + T cells predominate during the acute phase of pulmonary HSV-1 infection (Reading et al, 2006). Following i.n.…”

“…Sporadic virus replication was detected in TG 3-5 days post-infection (p.i.) (data not shown) and latent infection was established in TG of all infected animals (Reading et al, 2006(Reading et al, , 2007.…”

“…), consistent with our previous studies demonstrating that natural killer (NK) cells and CD8 + T cells predominate in the airways after i.n. HSV-1 infection (Reading et al, 2006(Reading et al, , 2007. Neutrophils comprised ,10 % of leukocytes in cell suspensions from pooled TG samples at days 3, 5 and 7 p.i.…”

The role of chemokines during herpes simplex virus-1 infection

“…Failure at any step in this process results in uncontrolled viral replication leading to herpes simplex encephalitis (56)(57)(58)(59). Conversely, effective innate control of viral replication may lower latent viral burden present in sensory ganglia, and reduce the frequency of subsequent reactivation.…”

IL-18, but not IL-12, Regulates NK Cell Activity following Intranasal Herpes Simplex Virus Type 1 Infection

“…In some assays lung cell suspensions were stimulated with an equivalent concentration of irrelevant peptide (SIINFEKL, OVA 257-264 ) under similar conditions. To detect intracellular IFN-␥ from NK cells, BALF cells were stained with anti-mouse IFN-␥ as described (7). To detect intracellular granzyme B, BALF cells were stained with CD3-FITC and NK1.1-PE, fixed and permeabilized before staining with allophycocyanin-conjugated anti-human granzyme B (Caltag Laboratories).…”