Hastings Cody James, Himmler Grace Elizabeth, Patel Arpeet, Marques Cláudia Nogueira Hora
Department of Biological Sciences, Binghamton University, Binghamton, NY, 13902.
Binghamton Biofilm Research Center, Binghamton University, Binghamton, NY, 13902.
bioRxiv. 2023 Jan 8:2023.01.07.523056. doi: 10.1101/2023.01.07.523056.
Bacterial persister cells - a metabolically dormant subpopulation tolerant to antimicrobials - contribute to chronic infections and are thought to evade host immunity. In this work, we studied the ability of persister cells to withstand host innate immunity. We found that persister cells resist MAC-mediated killing by the complement system despite being bound by complement protein C3b at levels similar to regular vegetative cells, in part due to reduced bound C5b - and are engulfed at a lower rate (10-100 fold), even following opsonization. Once engulfed, persister cells resist killing and, contrary to regular vegetative cells which induce a M1 favored (CD80+/CD86+/CD206-, high levels of CXCL-8, IL-6, and TNF-α) macrophage polarization, they initially induce a M2 favored macrophage polarization (CD80+/CD86+/CD206+, high levels of IL-10, and intermediate levels of CXCL-8, IL-6, and TNF-α), which is skewed towards M1 favored polarization (high levels of CXCL-8 and IL-6, lower levels of IL-10) by 24 hours of infection, once persister cells awaken. Overall, our findings further establish the ability of persister cells to evade the innate host response and to contribute chronic infections.
细菌持留细胞——一种对抗菌药物具有代谢耐受性的亚群——会导致慢性感染，并且被认为能够逃避宿主免疫。在这项研究中，我们研究了持留细胞抵抗宿主固有免疫的能力。我们发现，尽管持留细胞与补体蛋白C3b的结合水平与正常营养细胞相似，但它们能够抵抗补体系统介导的膜攻击复合物（MAC）杀伤，部分原因是结合的C5b减少，并且即使在调理作用后，其被吞噬的速率也较低（低10到100倍）。一旦被吞噬，持留细胞能够抵抗杀伤，与诱导M1型（CD80+/CD86+/CD206-，高水平的CXCL-8、IL-6和TNF-α）巨噬细胞极化的正常营养细胞相反，它们最初诱导M2型巨噬细胞极化（CD80+/CD86+/CD206+，高水平的IL-10，以及中等水平的CXCL-8、IL-6和TNF-α），但在感染24小时后，一旦持留细胞复苏，这种极化就会偏向M1型极化（高水平的CXCL-8和IL-6，低水平的IL-10）。总体而言，我们的研究结果进一步证实了持留细胞逃避宿主固有免疫反应并导致慢性感染的能力。
