Suppression of NK cells and regulatory T lymphocytes in cats naturally infected with feline infectious peritonitis virus

Abstract

A strong cell-mediated immunity (CMI) is thought to be indispensable for protection against infection with feline infectious peritonitis virus (FIPV) in cats. In this study, the role of natural killer (NK) cells and regulatory T cells (Tregs), central players in the innate and adaptive CMI respectively, was examined during natural FIPV infection. When quantified, both NK cells and Tregs were drastically depleted from the peripheral blood, mesenteric lymph node (LN) and spleen in FIP cats. In contrast, mesentery and kidney from FIP cats did not show any difference when compared to healthy non-infected control animals. In addition, other regulatory lymphocytes (CD4+CD25-Foxp3+ and CD3+CD8+Foxp3+) were found to be depleted from blood and LN as well. Phenotypic analysis of blood-derived NK cells in FIP cats revealed an upregulation of activation markers (CD16 and CD25) and migration markers (CD11b and CD62L) while LN-derived NK cells showed upregulation of only CD16 and CD62L. LN-derived NK cells from FIPV-infected cats were also significantly less cytotoxic when compared with healthy cats. This study reveals for the first time that FIPV infection is associated with severe suppression of NK cells and Tregs, which is reflected by cell depletion and lowered cell functionality (only NK cells). This will un-doubtfully lead to a reduced capacity of the innate immune system (NK cells) to battle FIPV infection and a decreased capacity (Tregs) to suppress the immunopathology typical for FIP. However, these results will also open possibilities for new therapies targeting specifically NK cells and Tregs to enhance their numbers and/or functionality during FIPV infection.

Enteric coronavirus infection in adult horses

“…The clinical outcome of the infection is affected by the development of humoral, cell-mediated or mixed immune responses against the highly virulent FIPV genotype of FCoV. Interestingly, severe suppression of natural killer cells and T regulatory cells is correlated with clinical outcome, confirming reports that fatal FIPV infection is associated with a weakened cell-mediated immune response (Vermeulen et al, 2013). Giannitti et al (2015) has recently described the pathology of ECoV in three adult equids.…”

Equine Coronavirus Infection

“…The development of a humoral, cell-mediated, or mixed immune response against the highly virulent FIPV version of FCoV distinctly influences the clinical outcome of the infection. Interestingly, the clinical outcome of FIPV has been correlated with a severe suppression of NK cells and T regulatory cells confirming earlier reports that a weakened cell-mediated immune response is associated with fatal FIPV infection (Vermeulen et al 2013).…”

Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection

“…' We did not determine the lymphocyte subclasses that were most affected although the severity of the lymphocyte depletion suggested that both T and B subsets were involved. However, previous studies indicate that T cells, NK cells and T regs are most severely reduced in cats with naturally and experimentally induced FIP (Dean et al, 2003;Vermeulen et al, 2013).…”

“…Lymphopenia is a consistent feature of both naturally (Pedersen, 2009(Pedersen, , 2014b and experimentally induced-FIP (Dean et al, 2003;de Groot-Mijnes et al, 2005). The role of lymphopenia in FIP has not been determined, but it has been equated with a decrease in cellular immunity and ultimate disease outcome in experimental infections (de Groot-Mijnes et al, 2005;Vermeulen et al, 2013). Although lymphopenia appears to play a role in FIP, temporal studies on the appearance, magnitude and duration of lymphopenia in cats that succumb or survive experimental infection have not been reported; most cell counts have been taken prior to infection and terminally.…”