Abstract
Containment of acute Toxoplasma gondii infection is dependent on an efficient interferon gamma response. However, the earliest steps of immune response initiation immediately following exposure to the parasite have not been previously characterized in pigs. Murine and human myeloid cells produce large quantities of interleukin (IL)-12 during early T. gondii infection. We therefore examined IL-12 expression by porcine peripheral blood monocytes and dendritic cell (DC) subsets following toll-like receptor (TLR) ligation and controlled T. gondii tachyzoite infection. We detected IL-12p40 expression by porcine plasmacytoid DC, but not conventional or monocyte-derived DC following TLR ligation. Unexpectedly, we also observed considerable IL-12p40 production by porcine CD3– NKp46+ cells—a classical natural killer cell phenotype—following TLR ligation. However, in response to T. gondii exposure, no IL-12 production was observed by either DC or CD3– NKp46+ cells. Despite this, IL-18 production by DC-enriched peripheral blood mononuclear cells was detected following live T. gondii tachyzoite exposure. Only combined stimulation of porcine peripheral blood mononuclear cells with recombinant IL-12p70 and IL-18 induced innate interferon gamma production by natural killer cells, while T cells and myeloid cells did not respond. Therefore, porcine CD3– NKp46+ cells serve as important IL-12 producers following TLR ligation, while IL-18 likely plays a prominent role in early immune response initiation in the pig following T. gondii infection.
Highlights
Toxoplasma gondii is an extremely widespread protozoan parasite, with a recent large meta-analysis examining data collected from pregnant women suggesting that 31.8–35.9%of this subgroup are seropositive for T. gondii globally [1]
NKp46+ cells serve as important IL-12 producers following toll-like receptor (TLR) ligation, while IL-18 likely plays a prominent role in early immune response initiation in the pig following T. gondii infection
We demonstrated that porcine plasmacytoid DC (pDC) are the only bona fide
Summary
Toxoplasma gondii is an extremely widespread protozoan parasite, with a recent large meta-analysis examining data collected from pregnant women suggesting that 31.8–35.9%of this subgroup are seropositive for T. gondii globally [1]. The major routes of human infection include consumption of water or raw vegetables which have been contaminated with oocysts originating from cat feces, or consumption of raw or undercooked meat containing tissue cysts [2]. Pork and mutton are the meats most commonly associated with transmission of T. gondii via tissue cysts, with another meta-analysis finding 12.3% of pork and 14.7% of mutton samples positive for T. gondii [2,3]. Despite the importance of T. gondii infections in pigs for public health, the porcine immune response to the parasite is relatively understudied. Interferon gamma (IFNγ) is the primary driver of resistance to acute T. gondii infection [5,6]. Rahman et al (2020) [7] demonstrated that peripheral blood mononuclear cells (PBMCs) isolated from T. gondii-infected pigs produce
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