SPI-1-encoded type III secretion system of Salmonella enterica is required for the suppression of porcine alveolar macrophage cytokine expression

Abstract

Genes localized at Salmonella pathogenicity island-1 (SPI-1) are involved in Salmonella enterica invasion of host non-professional phagocytes. Interestingly, in macrophages, SPI-1-encoded proteins, in addition to invasion, induce cell death via activation of caspase-1 which also cleaves proIL-1β and proIL-18, precursors of 2 proinflammatory cytokines. In this study we were therefore interested in whether SPI-1-encoded type III secretion system (T3SS) may influence proinflammatory response of macrophages. To test this hypothesis, we infected primary porcine alveolar macrophages with wild-type S. Typhimurium and S. Enteritidis and their isogenic SPI-1 deletion mutants. ΔSPI1 mutants of both serovars invaded approx. 5 times less efficiently than the wild-type strains and despite this, macrophages responded to the infection with ΔSPI1 mutants by increased expression of proinflammatory cytokines IL-1β, IL-8, TNFα, IL-23α and GM-CSF. Identical macrophage responses to that induced by the ΔSPI1 mutants were also observed to the infection with sipB but not the sipA mutant. The hilA mutant exhibited an intermediate phenotype between the ΔSPI1 mutant and the wild-type S. Enteritidis. Our results showed that the SPI-1-encoded T3SS is required not only for cell invasion but in macrophages also for the suppression of early proinflammatory cytokine expression.

Characterisation of basal expression of selected cytokines in the liver, spleen, and respiratory, reproductive and intestinal tract of hens

“…IL-22 was expressed at relatively low levels in all tissues consistent with its role in tissue protection during infection (Wolk et al, 2004). In mammals, major TNFα producers are recruited from activated mononuclear cells and macrophages (Henter et al, 1988;Cron et al, 1989;Pavlova et al, 2011). This is consistent with our findings that LITAF (a functional homologue of TNFα in chickens) was expressed highly in all mucosal tissues and spleen, but at very low levels in blood and magnum.…”

“…In our previous studies we also characterised cytokine gene expression using fold inductions Pavlova et al, 2011). However, we have noted that the basal expression in control groups differed considerably based on the type of tissue used for the analysis.…”

Identification of a Novel Francisella tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response

“…Several bacterial pathogens have evolved sophisticated mechanisms to subvert the host immune response by suppressing NF-B activity either at the level of IB phosphorylation or nuclear translocation. Mycobacterium, E. coli, and Brucella secrete effector proteins homologous to Toll/IL-1R domains (7,8,50,51), whereas Salmonella (52,53) and Chlamydia (54) utilize their secretion systems to inject effector proteins that interfere with the host ubiquitin signaling pathways to suppress IB ubiquitination and NF-B activity. In addition to NF-B, some bacterial pathogens have evolved mechanisms to suppress MAPKs, another key antimicrobial signaling pathway involved in bacterial clearance.…”

Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro

“…GCC TGG ACC TCA GTC ACA ACT This study CD14-Rev AGC GAA TGA CAA ATT GAG AGA GC This study CD163-For CTT GGG GCA GCG TTG GCA GGA ATA G (Kyrova et al, 2012) CD163-Rev ATG CAG GGC TGA TGT CCC CTC TGT C (Kyrova et al, 2012) CD80-For AAT GGT CAA AGC TGA CTT TCC TG (Volf et al, 2012) CD80-Rev GGT TGA GCA CCT TAT CCT TTT GA (Volf et al, 2012) HPRT-For GAG CTA CTG TAA TGA CCA GTC AAC G (Zelnickova et al, 2008) HPRT-Rev CCA GTG TCA ATT ATA TCT TCA ACA ATC AA (Zelnickova et al, 2008) IL-1b-For ATG CTG AAG GCT CTC CAC CTC (Von der Hardt et al, 2004) IL-1b-Rev TTG TTG CTA TCA TCT CCT TGC AC (Von der Hardt et al, 2004) IL-8-For TTC TGC AGC TCT CTG TGA GGC (Von der Hardt et al, 2004) IL-8-Rev GGT GGA AAG GTG TGG AAT GC (Von der Hardt et al, 2004) IL-10-For TGA AGA GTG CCT TTA GCA AGC TC (Kyrova et al, 2012) IL-10-Rev CTC ATC TTC ATC GTC ATG TAG GC (Kyrova et al, 2012) MannR-For GAC CAA AAA TTG TTG ATG CTG A (Kyrova et al, 2012) MannR-Rev GCA CCC GTT AGA ATC AGG AG (Kyrova et al, 2012) TLR4-For GTG CTG GAT TTA TCC AGA TGT GA (Volf et al, 2012) TLR4-Rev GAT TTC CCG TCA GTA TCA AGG TG (Volf et al, 2012) TNF-a-For CCC CCA GAA GGA AGA GTT TC (Pavlova et al, 2011) TNF-a-Rev CGG GCT TAT CTG AGG TTT GA(Pavlova et al, 2011) …”