Human polymorphonuclear leukocyte-mediated cytotoxicity against varicella-zoster virus-infected fibroblasts

Abstract

Polymorphonuclear leukocytes (PMN) were studied for their ability to mediate cytotoxicity against varicellazoster virus (VZV)-infected and uninfected human fibroblasts in 51Cr release assays. PMN were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) against VZV-infected targets. Maximal ADCC was obtained with effector-to-target ratios of 100:1 and 18 h of incubation. Percent 51Cr release for 26 normal adults was 14.1 ± 0.6 (mean ± standard error) in the presence of pooled human seropositive sera (final dilution, 1:100) and 0.5 ± 0.6 in the presence of pooled human seronegative sera. Addition of phorbol myristate acetate (PMA) enhanced PMN-mediated cytotoxicity against VZV-infected and uninfected targets. PMA-stimulated cytotoxicity was optimal with PMA concentrations of 200 ng/mI and effector-to-target ratios of 10:1, and antibody was not required; killing was detected as early as 3 h after incubation and was maximal after 18 h. Highly purified PMN were capable of mediating both ADCC and PMA-stimulated lysis. Catalase completely inhibited PMA-stimulated PMN cytotoxicity, but had no effect on PMN-mediated ADCC. PMN from patients with chronic granulomatous disease were capable of mediating ADCC, but not PMA-stimulated killing, against VZV-infected targets. Thus, PMN could kill VZV-infected targets by two different mechanisms: ADCC, which required antibody but not hydrogen peroxide (H202), and PMA-stimulated cytotoxicity, which required H202 but not antibody.

Monocytes Latently Infected with Human Cytomegalovirus Evade Neutrophil Killing

“…The ability of a pathogen to limit its visibility to multiple branches of the innate immune system is one immune evasion strategy often employed by pathogens and, in particular, those pathogens that establish latent or persistent infections, and this also includes avoidance of neutrophil killing. ADCC-mediated killing of virally infected cells by neutrophils has been reported for a number of viruses (Ackerman et al., 2016, Ashkenazi and Kohl, 1990, Bradford et al., 1992, Chai et al., 2017, Ihara et al., 1986, Siebens et al., 1979, Smalls-Mantey et al., 2013, Veillette et al., 2015). However, except for vaccinia virus, which is known to express a protein that interferes with this (Al-Mohanna et al., 2001), little has been reported on the strategies by which other viruses evade neutrophil killing.…”

rVSV(MΔ51)-M3 Is an Effective and Safe Oncolytic Virus for Cancer Therapy

“…Neutrophils may also act indirectly by producing cytokines (Lloyd and Oppenheim, 1992;Cassatella, 1995), which in turn recruit other effector cells, such as T cells, NK cells, and macrophages, to the site of viral infection. Finally, neutrophils may collaborate with other defensive factors such as antibody (Siebens et al, 1979;Hashimoto et al, 1983;Ihara et al, 1984) or complement (Tsuru et al, 1987) to kill virus-infected cells via cellular cytoxicity reactions. It has been proposed that their recruitment is also important in inhibiting virus propagation early during infection (Schall et al, 1994).…”

The interaction of neutrophils with respiratory epithelial cells in viral infection

“…Thus, neutrophils could kill VZV‐infected targets by two different mechanisms: ADCC, which required antibody but not hydrogen peroxide (H 2 O 2 ), and PMA‐stimulated cytotoxicity, which required H 2 O 2 but not antibody. 68 …”