Abstract
Saponin-based adjuvants have been widely used to enhance humoral and cellular immune responses in many species, but their mode of action is not fully understood. A characterization of the porcine transcriptional response to Matrix-M was performed in vitro using lymphocytes, monocytes or monocyte-derived dendritic cells (MoDCs) and in vivo. The effect of Matrix-M was also evaluated in specific pathogen free (SPF) pigs exposed to conventionally reared pigs. The pro-inflammatory cytokine genes IL1B and CXCL8 were up-regulated in monocytes and lymphocytes after Matrix-M exposure. Matrix-M also induced IL12B, IL17A and IFNG in lymphocytes and IFN-α gene expression in MoDCs. Several genes were indicated as up-regulated by Matrix-M in blood 18 h after injection, of which the genes for IFN-α and TLR2 could be statistically confirmed. Respiratory disease developed in all SPF pigs mixed with conventional pigs within 1–3 days. Two out of four SPF pigs injected with saline prior to contact exposure displayed systemic symptoms that was not recorded for the four pigs administered Matrix-M. Granulocyte counts, serum amyloid A levels and transcription of IL18 and TLR2 coincided with disease progression in the pigs. These results support further evaluation of Matrix-M as a possible enhancer of innate immune responses during critical moments in pig management.
Highlights
Immunostimulatory effects of saponins from Quillaja saponaria Molina are known since nearly 100 years
The conventionally reared pigs came from a farrow-to-finish herd with a high prevalence of respiratory lesions recorded at slaughter. Pigs in this herd were in general seronegative to Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Pasteurella multocida and Streptococcus suis when transferred to fattening units at 11 weeks of age, but displayed high levels of serum antibodies to A. pleuropneumoniae and to P. multocida 8 weeks later
Transcriptional response to Matrix‐M in vitro The transcriptional response in lymphocytes, monocytes and monocyte-derived dendritic cells (MoDCs) was measured after short-term (6 h) and long-term (3 or 5 days) stimulation with Matrix-M (Table 2)
Summary
Immunostimulatory effects of saponins from Quillaja saponaria Molina are known since nearly 100 years. Immunization experiments using Matrix-M as adjuvant reveal an antigen specific immune response characterized by long-lasting antibody production, a balanced TH1/TH2 cytokine profile and induction of cytotoxic T cells [7–9]. The innate immune reaction to intramuscular injection of Matrix-M in pigs was further characterized by a type I interferon-related transcriptional response both at the site of administration and in the draining lymph node [16, 20]. These indications that Matrix-M seems to activate the interferon system, amongst other innate immune parameters, raises the possibility for its strategic use in pigs that are extra vulnerable to infections
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