Abstract
Streptococcus suis serotype 2 (SS2), an important zoonotic pathogen that causes septicemia, arthritis, and irreversible meningitis in pigs and humans, can be transmitted to humans from pigs. S. suis causes huge economic losses to the swine industry and poses a serious threat to public health. Previously, we found that the brain tissues of mice with SS2-induced meningitis showed disrupted structural integrity and significantly enhanced polymorphonuclear neutrophil (PMN) infiltration. We showed that the brain tissues of SS2-infected mice had increased ribosomal protein SA (RPSA)-positive PMN counts. However, the inflammatory responses of RPSA+ PMNs to SS2 and their effects on the blood-brain barrier (BBB) remain unclear. Therefore, in studying the pathogenesis of SS2-induced meningitis, it is essential that we explore the functions of RPSA+ PMNs and their effects on the BBB. Herein, using flow cytometry and immunofluorescence microscopy analyses, we found that RPSA expression enhances PMN-induced phagocytosis and PMN-induced formation of neutrophil extracellular traps (NETs), which facilitate further elimination of bacteria. PMN surface expression of RPSA also alleviates local inflammation and tissue injuries by inhibiting secretion of the pro-inflammatory cytokines, TNF-α and IL-6. Moreover, the single-cell BBB model showed that RPSA disrupts BBB integrity by downregulating expression of tight junction-associated membrane proteins on PMNs. Taken together, our data suggest that PMN-surface expression of RPSA is a double-edged sword. RPSA+ PMN owns a stronger ability of bacterial cleaning and weakens inflammatory cytokines release which are useful to anti-infection, but does hurt BBB. Partly, RPSA+ PMN may be extremely useful to control the infection as a therapeutic cellular population, following novel insights into the special PMN population.
Highlights
Streptococcus suis infection is a zoonotic disease mainly attributable to S. suis, which is distributed worldwide, especially in countries with an extensive swine industry, and is highly prevalent in Africa and Southeast Asia [1]
The development of suis serotype 2 (SS2)-induced meningitis is mainly triggered by increased inflammatory responses in the central nervous system (CNS) following bacterial invasion of the brain tissues
Despite being the main innate immune cells implicated in the fight against bacterial infection, the defense mechanism(s) of neutrophils against SS2-induced meningitis remain unclear
Summary
Streptococcus suis infection is a zoonotic disease mainly attributable to S. suis, which is distributed worldwide, especially in countries with an extensive swine industry, and is highly prevalent in Africa and Southeast Asia [1]. There have been more than 1,500 reported cases of S. suis infections worldwide, of which the majority were reported in Thailand, followed by Vietnam. SS2 has caused huge economic losses to the swine industry and has become one of the major infectious diseases affecting the swine industry in China [4]. SS2 is a zoonotic pathogen that poses a significant threat to public health as it can be transmitted to humans from pigs via direct contact or consumption of undercooked infected pork, leading to diseases, such as bacterial endocarditis, meningitis, and toxic shock syndrome, and may even cause death in severe cases [5]. SS2 may cause bacterial meningitis in both pigs and humans, eventually resulting in severe central nervous system (CNS) lesions and death with a mortality rate of 68% [6, 7]. The effective prevention and treatment methods for S. suis-induced meningitis can be determined by exploring its pathogenesis
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