Inflammatory Monocytes and Neutrophils Regulate Streptococcus suis-Induced Systemic Inflammation and Disease but Are Not Critical for the Development of Central Nervous System Disease in a Mouse Model of Infection

Abstract

Streptococcus suis is an important porcine bacterial pathogen and zoonotic agent responsible for sudden death, septic shock, and meningitis. These pathologies are a consequence of elevated bacterial replication leading to exacerbated and uncontrolled inflammation, a hallmark of the S. suis systemic and central nervous system (CNS) infections. Monocytes and neutrophils are immune cells involved in various functions, including proinflammatory mediator production. Moreover, monocytes are composed of two main subsets: shorter-lived inflammatory monocytes and longer-lived patrolling monocytes. However, regardless of their presence in blood and the fact that S. suis-induced meningitis is characterized by infiltration of monocytes and neutrophils into the CNS, their role during the S. suis systemic and CNS diseases remains unknown. Consequently, we hypothesized that monocytes and neutrophils participate in S. suis infection via bacterial clearance and inflammation. Results demonstrated that inflammatory monocytes and neutrophils regulate S. suis-induced systemic disease via their role in inflammation required for bacterial burden control. In the CNS, inflammatory monocytes contributed to exacerbation of S. suis-induced local inflammation, while neutrophils participated in bacterial burden control. However, development of clinical CNS disease was independent of both cell types, indicating that resident immune cells are mostly responsible for S. suis-induced CNS inflammation and clinical disease and that inflammatory monocyte and neutrophil infiltration is a consequence of the induced inflammation. In contrast, the implication of patrolling monocytes was minimal throughout the S. suis infection. Consequently, this study demonstrates that while inflammatory monocytes and neutrophils modulate S. suis-induced systemic inflammation and disease, they are not critical for CNS disease development.

Neutrophils in Streptococcus suis Infection: From Host Defense to Pathology

“…Several chemokines potentially attract neutrophils during an infection and S. suis infection induces the production of many of them, such as CXCL1 (KC), CXCL2 (MIP-2), CCL2 (MCP-1), CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES) [7,77,85,86,133,145]. In vivo, neutrophil mobilization positively correlated with cytokine/chemokine levels in mouse and porcine models [77,140,145], but only one study established a causality between a cytokine and neutrophil mobilization [144]. Indeed, IL-17A caused neutrophil recruitment in infected mice, despite a minor role in overall S. suis-induced inflammation [144].…”

Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis

“…Because neutrophils are crucial mediators of host defenses during acute bacterial meningitis ( 21 ), neutrophil counts and myeloperoxidase (MPO) activity (an indirect indicator of neutrophil recruitment) in the brain after infection were assessed. Fpr2 deficiency increased neutrophil recruitment in the brain at 6 and 14 h after infection ( Fig.…”

“…The results of this study provide new insights into S. suis meningitis and uncover a distinct contribution of neutrophil recruitment to S. suis meningitis. Neutrophils are key regulatory cells of host defenses that are recruited to the CNS in great numbers during acute bacterial meningitis ( 21 ). It is known that the chromosomal pathogenicity island (PAI) designated SsPI-1 in Chinese epidemic S. suis strains is associated with human meningitis ( 30 ).…”

“…Meanwhile, exogenous AnxA1additionally alleviated inflammatory responses, as characterized by reduced bacterial loads and cytokine levels, migratory astrocyte and microglial responses, and granulocyte invasion, during S. suis meningitis in WT but not Fpr2 −/− mice. We also found that AnxA1 decreased neutrophil adhesion through Fpr2, and AnxA1 decreased IL-6 expression through the Fpr2/p38/COX-2 pathway, which may clarify the mechanism by which the protein decreased cytokine expression and brain damage during S. suis meningitis.on December 20, 2020 by guest http://iai.asm.org/Downloaded fromThe results of this study provide new insights into S. suis meningitis and uncover a distinct contribution of neutrophil recruitment to S. suis meningitis.Neutrophils are key regulatory cells of host defenses that are recruited to the CNS in great numbers during acute bacterial meningitis(21). It is known that the chromosomal pathogenicity island (PAI) designated SsPI-1 in Chinese epidemic S. suis strains is associate with human meningitis(30).…”

B cell activating factor (BAFF) from neutrophils and dendritic cells is required for protective B cell responses against Salmonella typhimurium infection

“…Innate immune cells such as Nphs, cDCs and MOs contribute to immunity against a number of infections, including Salmonella [ 20 , 44 – 47 ]. The role of innate immune cells goes far beyond pathogen killing and involves production of cytokines that critically link the innate and adaptive immune system [ 13 , 24 – 26 ].…”