Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis.
Necroptosis Contributes to Persistent Inflammation During Acute Leptospirosis.
复制标题
DOI：
10.3389/fimmu.2022.810834
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
Gomes-Solecki M
中科院分区：
文献类型：
--
作者：
Kundu S;Shetty A;Gomes-Solecki M
钩端螺旋体病是一种新兴的传染病。最近，加利福尼亚和纽约分别报告了犬和人钩端螺旋体病暴发。在这项研究中，我们评估了细胞死亡过程在钩端螺旋体的炎症反应中所起的作用。雄性C3H/HeJ小鼠分别感染致病性疑问乳杆菌和非致病性双歧乳杆菌24和72小时；通过脾细胞流式细胞术表征炎症过程中的凋亡和坏死坏死，并通过western blot进一步评估坏死坏死生物标志物的表达。我们发现致病性疑问乳杆菌在感染后24小时和72小时促进髓系中性粒细胞和单核细胞的凋亡，而双歧杆菌仅在感染后24小时促进髓系单核细胞的凋亡。有趣的是，在我们之前的研究中，经历常见的程序性细胞死亡途径（凋亡）的免疫细胞是在中性粒细胞和单核细胞感染L.疑问菌（L.疑问菌）小鼠脾脏中频率未增加的细胞类型。致病性疑问乳杆菌在感染后24小时和/或72小时诱导骨髓中性粒细胞和单核细胞和巨噬细胞坏死，而双歧杆菌仅在感染后24小时促进单核细胞和巨噬细胞的这种促炎细胞死亡过程。因此，这些细胞类型的早期凋亡和坏死下垂可能解释了其在脾脏中频率的减少。此外，在感染致病性疑问乳杆菌24和72h时，坏死下垂分子标志物p-MLKL、p-RIP1和p-RIP3的表达增加。这些数据表明，参与致病性钩端螺旋体免疫应答的潜在细胞死亡过程直接导致钩端螺旋体病早期阶段的持续炎症。
Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbreaks were reported in California and New York, respectively. In this study we evaluated the role that cell death processes play in the inflammatory response to Leptospira. Groups of male C3H/HeJ mice were infected with pathogenic L. interrogans and non-pathogenic L. biflexa for 24 and 72 hours; inflammatory processes were characterized for apoptosis and necroptosis by flowcytometry of spleen cells and were further assessed for expression of biomarkers of necroptosis by western blot. We found that pathogenic L. interrogans promotes apoptosis in myeloid neutrophils and monocytes at 24h and 72h post-infection, whereas L. biflexa promotes apoptosis of myeloid monocytes only at 24h post-infection. It is interesting that the immune cells undergoing the common programmed cell death pathway (apoptosis) are the cell types which were not increased in frequency in spleen of mice infected with L. interrogans (neutrophils) and L. biflexa (monocytes) in our previous study. The same trend was observed with pathogenic L. interrogans inducing necroptosis of myeloid neutrophils in addition to monocytes and macrophages at 24h and/or 72h post-infection, whereas L. biflexa promoted this pro-inflammatory cell death process in monocytes and macrophages only at 24h post-infection. Thus, early apoptosis and necroptosis of these cell types may explain its absence in frequency in spleen. Furthermore, at 24h and 72h, expression of the necroptosis molecular biomarkers p-MLKL, p-RIP1 and p-RIP3 was increased post infection with pathogenic L. interrogans. These data suggest that the underlying cell death processes involved in immune responses to pathogenic Leptospira contribute directly to persistent inflammation during the early stages of leptospirosis.
登录
查看更多内容
影响因子：
5.7
作者：
Shetty A;Kundu S;Gomes-Solecki M
通讯作者：
Gomes-Solecki M
影响因子：
3.1
作者：
Gomes, Charles K.;Guedes, Mariana;Gomes-Solecki, Maria
通讯作者：
Gomes-Solecki, Maria
DOI：
10.1186/s40409-015-0022-y
发表时间：
2015
期刊：
The journal of venomous animals and toxins including tropical diseases
影响因子：
--
作者：
Marinho M;Táparo CV;Oliveira-Júnior IS;Perri SH;Cardoso TC
通讯作者：
Cardoso TC
影响因子：
3.1
作者：
Sullivan, Joseph Pierce;Nair, Nisha;Gomes-Solecki, Maria
通讯作者：
Gomes-Solecki, Maria
影响因子：
6
作者：
Paolini A;Borella R;De Biasi S;Neroni A;Mattioli M;Lo Tartaro D;Simonini C;Franceschini L;Cicco G;Piparo AM;Cossarizza A;Gibellini L
通讯作者：
Gibellini L