Explore the vast range of titles available.

The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs ( P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs ( P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs ( P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs ( P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs ( P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.

The porcine pathogen and zoonotic agent Streptococcus suis induces an exacerbated inflammation in the infected hosts that leads to sepsis, meningitis, and sudden death. Several virulence factors were described for S . suis of which the capsular polysaccharide (CPS) conceals it from the immune system, and the suilysin exhibits cytotoxic activity. Although neutrophils are recruited rapidly upon S . suis infection, their microbicidal functions appear to be poorly activated against the bacteria. However, during disease, the inflammatory environment could promote neutrophil activation as mediators such as the granulocyte colony-stimulating factor granulocyte (G-CSF) and the granulocyte-macrophages colony-stimulating factor (GM-CSF) prime neutrophils and enhance their responsiveness to bacterial detection. Thus, we hypothesized that CPS and suilysin prevent an efficient activation of neutrophils by S . suis , but that G-CSF and GM-CSF rescue neutrophil activation, leading to S . suis elimination. We evaluated the functions of porcine neutrophils in vitro in response to S . suis and investigated the role of the CPS and suilysin on cell activation using isogenic mutants of the bacteria. We also studied the influence of G-CSF and GM-CSF on neutrophil response to S . suis by priming the cells with recombinant proteins. Our study confirmed that CPS prevents S . suis -induced activation of most neutrophil functions but participates in the release of neutrophil-extracellular traps (NETs). Priming with G-CSF did not influence cell activation, but GM-CSF strongly promote IL-8 release, indicating its involvement in immunomodulation. However, priming did not enhance microbicidal functions. Studying the interaction between S . suis and neutrophils–first responders in host defense–remains fundamental to understand the immunopathogenesis of the infection and to develop therapeutical strategies related to neutrophils’ defense against this bacterium.

Streptococcus suis is a swine pathogen and zoonotic agent responsible for economic losses to the porcine industry. Infected animals may develop meningitis, arthritis, endocarditis, sepsis and/or sudden death. The pathogenesis of the infection implies that bacteria breach mucosal host barriers and reach the bloodstream, where they escape immune-surveillance mechanisms and spread throughout the organism. The clinical manifestations are mainly the consequence of an exacerbated inflammation, defined by an exaggerated production of cytokines and recruitment of immune cells. Among them, neutrophils arrive first in contact with the pathogens to combat the infection. Neutrophils initiate and maintain inflammation, by producing cytokines and deploying their arsenal of antimicrobial mechanisms. Furthermore, neutrophilic leukocytosis characterizes S. suis infection, and lesions of infected subjects contain a large number of neutrophils. Therefore, this cell type may play a role in host defense and/or in the exacerbated inflammation. Nevertheless, a limited number of studies addressed the role or functions of neutrophils in the context of S. suis infection. In this review, we will explore the literature about S. suis and neutrophils, from their interaction at a cellular level, to the roles and behaviors of neutrophils in the infected host in vivo.

Streptococcus suis causes diseases in pigs and has emerged as a zoonotic agent. When infected, the host develops an exacerbated inflammation that can lead to septic shock and meningitis. Although neutrophils greatly infiltrate the lesions, their dynamics during S. suis infection remain poorly described. Moreover, very few studies reported on the production and role of a key factor in the regulation of neutrophils: the colony-stimulating granulocyte factor (G-CSF). In this study, we characterized the G-CSF-neutrophil axis in the pathogenesis of S. suis induced disease. Using a mouse model of S. suis infection, we first evaluated the recruitment of neutrophils and their activation profile by flow cytometry. We found that infection provokes a massive neutrophil recruitment from the bone marrow to the blood and spleen. In both compartments, neutrophils displayed multiple activation markers. In parallel, we observed high systemic levels of G-CSF, with a peak of production coinciding with that of neutrophil recruitment. We then neutralized the effects of G-CSF and highlighted its role in the release of neutrophils from the bone marrow to the blood. However, it did not affect bacteremia nor the cytokine storm induced by S. suis . In conclusion, systemic G-CSF induces the release of neutrophils from the bone marrow to the blood, but its role in inflammation or bacterial clearance seems to be compensated by unknown factors. A better understanding of the role of neutrophils and inflammatory mediators could lead to better strategies for controlling the infection caused by S. suis.

IntroductionExcessive activation of the adenosine A2A receptor (A2AR) contributes to chronic neuroinflammation, in part through spatial coupling with the adenosine-generating enzyme CD73, which enables localized adenosine signaling. Coordinated regulation of Nt5e and Adora2a across neuropathological conditions supports dual targeting of the CD73/A2AR axis to constrain maladaptive inflammatory signaling.MethodsPrimary rat astrocytes were exposed to TNF-α, IL-1α, and C1q (TIC) to induce a neurotoxic reactive astrocyte (nRA) substate. Concomitant pharmacological inhibition of CD73 (APCP, 100 μM) and A2AR (istradefylline, 10 μM) was applied. Morphological, redox, inflammatory, and functional outcomes were assessed, including CD73 expression and activity, CD73/A2AR spatial proximity, cytokine release, and astrocyte-mediated neurotoxicity.ResultsDual CD73/A2AR blockade attenuated key features of the nRA phenotype, including astrocyte hypertrophy, oxidative stress, and impaired antioxidant capacity. These effects were associated with normalization of CD73 expression and activity, reduced spatial proximity between CD73 and A2AR, suppression of IL-1β release and complement- and immune cell-recruiting effector programs (C3, VCAM1), and modulation of redox-sensitive pathways ( Nos2 /NO, NRF2). Notably, IL-6- and TNFα-driven core inflammatory signaling remained preserved. Functionally, dual blockade shifted astrocytes toward a less neurotoxic phenotype, reducing their impact on neuronal Ca2+ homeostasis and improving neuronal viability.DiscussionThese findings demonstrate that dual CD73/A2AR blockade selectively reconfigures astrocyte inflammatory networks under the tested conditions, without broadly suppressing inflammatory or homeostatic functions at the examined time point. This supports the CD73/A2AR axis as a promising therapeutic target for limiting chronic astrocyte-driven neurotoxicity.

Excessive activation of the adenosine A receptor (A R) contributes to chronic neuroinflammation, in part through spatial coupling with the adenosine-generating enzyme CD73, which enables localized adenosine signaling. Coordinated regulation of and across neuropathological conditions supports dual targeting of the CD73/A R axis to constrain maladaptive inflammatory signaling. Primary rat astrocytes were exposed to TNF-α, IL-1α, and C1q (TIC) to induce a neurotoxic reactive astrocyte (nRA) substate. Concomitant pharmacological inhibition of CD73 (APCP, 100 μM) and A R (istradefylline, 10 μM) was applied. Morphological, redox, inflammatory, and functional outcomes were assessed, including CD73 expression and activity, CD73/A R spatial proximity, cytokine release, and astrocyte-mediated neurotoxicity. Dual CD73/A R blockade attenuated key features of the nRA phenotype, including astrocyte hypertrophy, oxidative stress, and impaired antioxidant capacity. These effects were associated with normalization of CD73 expression and activity, reduced spatial proximity between CD73 and A R, suppression of IL-1β release and complement- and immune cell-recruiting effector programs (C3, VCAM1), and modulation of redox-sensitive pathways ( /NO, NRF2). Notably, IL-6- and TNFα-driven core inflammatory signaling remained preserved. Functionally, dual blockade shifted astrocytes toward a less neurotoxic phenotype, reducing their impact on neuronal Ca homeostasis and improving neuronal viability. These findings demonstrate that dual CD73/A R blockade selectively reconfigures astrocyte inflammatory networks under the tested conditions, without broadly suppressing inflammatory or homeostatic functions at the examined time point. This supports the CD73/A R axis as a promising therapeutic target for limiting chronic astrocyte-driven neurotoxicity.