Early disruption of the innate-adaptive immune axis in vivo after infection with virulent Georgia2007/1 ASFV

Abstract

Effective immune defence and pathogen clearance requires coordination between innate and adaptive immune responses. However, virulent African swine fever virus (ASFV), which has a high case fatality rate in pigs, causes severe disease by exploiting multiple immune evasion strategies to suppress host responses. The global spread of Georgia2007/1 and its derivatives poses a significant threat to the pig industry and global food security. Although modified live virus vaccines for ASF exist, multiple safety concerns have restricted their use internationally. Conversely, subunit vaccine candidates have not matched the protective efficacy of modified live virus vaccines. This highlights the need to further investigate ASFV-induced immunopathology to support the development of next-generation ASF vaccines. Immune dynamics in whole blood and lymphoid tissues were examined over time after oronasal infection with Georgia 2007/1. CD4+ T cells, {gamma}{delta}-TCR+ T cells and CD21+ B cells were impacted by lymphopenia, and initial immune activation was detected. However, as the disease progressed, impaired maintenance and depletion of adaptive immune cells, such as CD4+ T cells and professional antigen-presenting dendritic cells and macrophages was observed. This depletion of cells may have compromised the innate-adaptive immune axis, weakening host ability to mount a robust adaptive immune response and potentially contributing to disease progression. Differential ASFV infection profiles within the spleen were also detected, highlighting the diversity of ASFV cellular tropism. Further investigation into the innate-adaptive immune axis is needed to better understand its role in ASFV infection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/660190v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@12b96a4org.highwire.dtl.DTLVardef@af2722org.highwire.dtl.DTLVardef@13237e4org.highwire.dtl.DTLVardef@1f371f1_HPS_FORMAT_FIGEXP M_FIG C_FIG