Analyses of the Impact of Immunosuppressive Cytokines on Porcine Macrophage Responses and Susceptibility to Infection to African Swine Fever Viruses

Abstract

African swine fever viruses (ASFV), currently a serious threat to the global pig industry, primarily target porcine macrophages. Macrophages are characterized by their remarkable plasticity, being able to modify their phenotype and functions in response to diverse stimuli. Since IL-10 and TGF-β polarize macrophages toward an anti-inflammatory phenotype, we analyzed their impact on porcine monocyte-derived macrophages’ (moMΦ) susceptibility to infection and their responses to two genotype I ASFV strains, virulent 26544/OG10 and attenuated NH/P68. At a low multiplicity of infection (MOI), NH/P68, but not 26544/OG10, presented a higher ability to infect moM(IL-10) compared to moMΦ and moM(TGF-β), but no differences were appreciated at a higher MOI. Both strains replicated efficiently in all moMΦ subsets, with no differences at later times post-infection. Both strains downregulated CD14 and CD16 expression on moMΦ, irrespective of the activation status. ASFV’s modulation of CD163 and MHC II DR expression and cytokine responses to NH/P68 or 26544/OG10 ASFV were not affected by either IL-10 or TGF-β pre-treatment. Our results revealed little impact of these anti-inflammatory cytokines on moMΦ interaction with ASFV, which likely reflects the ability of the virus to effectively modulate macrophage responses.

Adenovirus-Vectored African Swine Fever Virus pp220 Induces Robust Antibody, IFN-γ, and CTL Responses in Pigs

“…Immunization of pigs with a five-antigen cocktail that included adenoviruses expressing the pp220 antigens conferred protection in 5/9 pigs following challenge ( 57 ). Induction of CTLs capable of eliminating infected cells could be the key to complete protection since ASFV-infected cells are cleared specifically by CTLs induced by live-attenuated ASFV ( 31 , 33 ). It has previously been shown that CD8 + cells from pigs that recovered from ASFV infection are cytotoxic to macrophages infected with vaccinia virus expressing the p32 antigen ( 81 ).…”

“…Most naïve animals infected with highly virulent ASFV succumb to the disease before the immune system can intervene ( 29 , 30 ). Macrophages, monocytes, and to some extent DCs support ASFV replication, and the impaired APC functions are potential mechanisms of immune evasion ( 31 – 33 ). Infection occurs via the upper respiratory tract where the virus replicates in tonsils and drains to lymph nodes in the head and neck region.…”

“…Cross-talk between innate and adaptive immune responses is facilitated in the lymph nodes, which makes the regions they drain ideal sites for immunization with ASF vaccines ( 34 – 37 ). The draining lymph nodes are key to the development of mature B cells, cytotoxic T lymphocytes (CTLs), and natural killer (NK) cells, which are involved in the clearance of infected cells ( 33 , 38 – 41 ).…”

“…A connection between IFN-γ secretion and CD8 + T-cell activity has been observed in several studies in response to antigenic stimulation or natural infection. Thus, IFN-γ response and CTL activities are logical indicators of immune responses to vaccination ( 33 , 50 , 51 ). However, IFN-γ levels may not reflect protection since the cytokine can be produced by macrophages, CD4 + , CD8 + , γδ + T cells, innate B cells, and NK cells on antigen activation ( 31 , 33 , 43 ).…”

“…Thus, IFN-γ response and CTL activities are logical indicators of immune responses to vaccination ( 33 , 50 , 51 ). However, IFN-γ levels may not reflect protection since the cytokine can be produced by macrophages, CD4 + , CD8 + , γδ + T cells, innate B cells, and NK cells on antigen activation ( 31 , 33 , 43 ).…”