Young Sang Hwang, Ji-Hun Shin, Jung-Pyo Yang, Bong-Kwang Jung, Sang Hyung Lee, Eun-Hee Shin
Abstract
To examine the immune environment of chronicToxoplasma gondiiinfection in the brain, the characteristics of infection-immunity (premunition) in infection withT.gondiistrain ME49 were investigated for 12 weeks postinfection (PI). The results showed that neuronal cell death, microglia infiltration and activation, inflammatory and anti-inflammatory cytokine expression, Stat1 phosphorylation, and microglia activation and inflammatory gene transcripts related to M1 polarization in the brain were increased during the acute infection (AI) stage (within 6 weeks PI), suggesting that innate and cellular inflammatory response activation and neurodegeneration contributed to excessive inflammatory responses. However, these immune responses decreased during the chronic infection (CI) stage (over 6 weeks PI) with reductions in phosphorylated STAT1 (pSTAT1) and eosinophilic neurons. Notably, increases were observed in transcripts of T-cell exhaustion markers (TIM3, LAG3, KLRG1, etc.), suppressor of cytokines signaling 1 protein (SOCS1), inhibitory checkpoint molecules (PD-1 and PD-L1), and Arg1 from the AI stage (3 weeks PI), implying active immune intervention under the immune environment of M1 polarization of microglia and increases in inflammatory cytokine levels. However, when BV-2 microglia were stimulated withT. gondiilysate antigens (strain RH or ME49)in vitro, nitrite production increased and urea production decreased. Furthermore, when BV-2 cells were infected byT. gondiitachyzoites (strain RH or ME49)in vitro, nitric oxide synthase and COX-2 levels decreased, whereas Arg1 levels significantly increased. Moreover, Arg1 expression was higher in ME49 infection than in RH infection, whereas nitrite production was lower in ME49 infection than in RH infection. Accordingly, these results strongly suggest that immune triggering ofT. gondiiantigens induces M1 polarization and activation of microglia as well as increase NO production, whereasT.gondiiinfection induces the inhibition of harmful inflammatory responses, even with M1 polarization and activation of microglia and Th1 inflammatory responses, suggesting a host-parasite relationship through immune regulation during CI. This is a characteristic of infection immunity in infection withT. gondiiin the central nervous system, and SOCS1, a negative regulator of toxoplasmic encephalitis, may play a role in the increase in Arg1 levels to suppress NO production.
Pharmacology, Toxicology and Pharmaceutical Science
2
4%
Other
5
9%
Unknown
15
26%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 March 2018.
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#16,725,651
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#18,341
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Outputs of similar age from Frontiers in immunology
#435
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