Lavagna Agustina, Auger Jean-Philippe, Girardin Stephen E, Gisch Nicolas, Segura Mariela, Gottschalk Marcelo
Research Group on Infectious Diseases in Production Animals & Swine and Poultry Infectious Diseases Research Centre, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, QC J2S 2M2, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M58 1A8, Canada.
Pathogens. 2020 Feb 21;9(2):147. doi: 10.3390/pathogens9020147.
serotype 2 is an important porcine bacterial pathogen and zoonotic agent causing sudden death, septic shock and meningitis. These pathologies are the consequence of an exacerbated inflammatory response composed of various mediators including interleukin (IL)-1β. Elevated levels of the toxin suilysin (SLY) were demonstrated to play a key role in -induced IL-1β production. However, 95% of serotype 2 strains isolated from diseased pigs in North America, many of which are virulent, do not produce SLY. In this study, we demonstrated that SLY-negative induces elevated levels of IL-1β in systemic organs, with dendritic cells contributing to this production. SLY-negative -induced IL-1β production requires MyD88 and TLR2 following recognition of lipoproteins. However, the higher internalization rate of the SLY-negative strain results in intracellularly located DNA being recognized by the AIM2 inflammasome, which promotes IL-1β production. Finally, the role of IL-1 in host survival during the systemic infection is beneficial and conserved, regardless of SLY production, via modulation of the inflammation required to control bacterial burden. In conclusion, this study demonstrates that SLY is not required for -induced IL-1β production.
2型血清型是一种重要的猪源细菌病原体和人畜共患病原体,可导致猝死、感染性休克和脑膜炎。这些病症是由包括白细胞介素(IL)-1β在内的多种介质组成的炎症反应加剧的结果。毒素溶素(SLY)水平升高被证明在诱导IL-1β产生中起关键作用。然而,从北美患病猪中分离出的95%的2型血清型菌株,其中许多具有毒性,并不产生SLY。在本研究中,我们证明SLY阴性菌株在全身器官中诱导IL-1β水平升高,树突状细胞参与了这种产生过程。SLY阴性菌株诱导的IL-1β产生在识别脂蛋白后需要MyD88和TLR2。然而,SLY阴性菌株较高的内化率导致细胞内定位的DNA被AIM2炎性小体识别,从而促进IL-1β的产生。最后,无论SLY的产生情况如何,IL-1在全身感染期间对宿主存活的作用都是有益的且保守的,通过调节控制细菌负荷所需的炎症来实现。总之,本研究表明SLY不是诱导IL-1β产生所必需的。