Similar Datasets
Project description:Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. T cells preferentially home to the brain, but not other tissue sites, during Staphylococcus aureus (S. aureus) craniotomy infection; however, their functional importance is unknown. CD4+ T cells were critical for bacterial containment during craniotomy infection as Rag1-/- mice and WT animals treated with anti-CD4 or VLA-4 and LFA-1 antibodies exhibited elevated bacterial burdens. scRNA-seq revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent and typified by both Th1 and Th17 signatures, and adoptive transfer of either subset in Rag1-/- mice prevented S. aureus outgrowth. scRNA-seq revealed a profound IFN-γ signature in innate immune cells from Rag1-/- mice during craniotomy infection, supporting extensive T cell-innate immune crosstalk that was validated by immunostaining in the brain parenchyma. A cooperative role for Th1 and Th17 driven responses was demonstrated by treatment of Ifng-/- mice with IL-17A/F neutralizing Ab that recapitulated phenotypes observed in Rag1-/- animals, which were not observed following the loss of either cytokine alone. Collectively, these results implicate a critical role for CD4+ T cells in S. aureus containment during craniotomy infection by shaping the innate immune landscape.
2024-11-25 | GSE264736 | GEO
Project description:Access to the brain for treating neurological sequalae requires a craniotomy, which can be complicated by infection. T cells preferentially home to the brain, but not other tissue sites, during Staphylococcus aureus (S. aureus) craniotomy infection; however, their functional importance is unknown. CD4+ T cells were critical for bacterial containment during craniotomy infection as Rag1-/- mice and WT animals treated with anti-CD4 or VLA-4 and LFA-1 antibodies exhibited elevated bacterial burdens. scRNA-seq revealed transcriptional heterogeneity in brain CD3+ infiltrates, with CD4+ cells most prominent and typified by both Th1 and Th17 signatures, and adoptive transfer of either subset in Rag1-/- mice prevented S. aureus outgrowth. scRNA-seq revealed a profound IFN-γ signature in innate immune cells from Rag1-/- mice during craniotomy infection, supporting extensive T cell-innate immune crosstalk that was validated by immunostaining in the brain parenchyma. A cooperative role for Th1 and Th17 driven responses was demonstrated by treatment of Ifng-/- mice with IL-17A/F neutralizing Ab that recapitulated phenotypes observed in Rag1-/- animals, which were not observed following the loss of either cytokine alone. Collectively, these results implicate a critical role for CD4+ T cells in S. aureus containment during craniotomy infection by shaping the innate immune landscape.
2024-11-25 | GSE264737 | GEO
Project description:CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus biofilm infection.
| PRJNA1103881 | ENA
Project description:CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus biofilm infection [CD3+ scRNA-seq]
| PRJNA1103931 | ENA
Project description:CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus biofilm infection [RAG KO scRNA-seq]
| PRJNA1103933 | ENA
Project description:Staphylococcus aureus has reemerged as an important human pathogen in recent decades. Although many infections caused by this microbial species persist through a biofilm mode of growth, little is known about how the host's adaptive immune system responds to these biofilm infections. In this study, S. aureus cells adhered to pins in culture and were subsequently inserted into the tibiae of C57BL/6 mice, with an infecting dose of 2 × 10? CFU. This model was utilized to determine local cytokine levels, antibody (Ab) function, and T cell populations at multiple time points throughout infection. Like human hosts, S. aureus implant infection was chronic and remained localized in 100% of C57BL/6 mice at a consistent level of approximately 10(7) CFU/gram bone tissue after day 7. This infection persisted locally for >49 days and was recalcitrant to clearance by the host immune response and antimicrobial therapy. Local inflammatory cytokines of the Th1 (interleukin-2 [IL-2], IL-12 p70, tumor necrosis factor alpha [TNF-?], and IL-1?) and Th17 (IL-6 and IL-17) responses were upregulated throughout the infection, except IL-12 p70, which dwindled late in the infection. In addition, Th1 Ab subtypes against a biofilm antigen (SA0486) were upregulated early in the infection, while Th2 Abs and anti-inflammatory regulatory T cells (Tregs) were not upregulated until later. These results indicate that early Th1 and Th17 inflammatory responses and downregulated Th2 and Treg responses occur during the development of a chronic biofilm implant infection. This unrestrained inflammatory response may cause tissue damage, thereby enabling S. aureus to attach and thrive in a biofilm mode of growth.
| S-EPMC3067568 | biostudies-literature
Project description:The Staphylococcus aureus biofilm mode of growth is associated with several chronic infections that are very difficult to treat due to the recalcitrant nature of biofilms to clearance by antimicrobials. Accordingly, there is an increasing interest in preventing the formation of S. aureus biofilms and developing efficient antibiofilm vaccines. Given the fact that during a biofilm-associated infection, the first primary interface between the host and the bacteria is the self-produced extracellular matrix, in this study we analyzed the potential of extracellular proteins found in the biofilm matrix to induce a protective immune response against S. aureus infections. By using proteomic approaches, we characterized the exoproteomes of exopolysaccharide-based and protein-based biofilm matrices produced by two clinical S. aureus strains. Remarkably, results showed that independently of the nature of the biofilm matrix, a common core of secreted proteins is contained in both types of exoproteomes. Intradermal administration of an exoproteome extract of an exopolysaccharide-dependent biofilm induced a humoral immune response and elicited the production of interleukin 10 (IL-10) and IL-17 in mice. Antibodies against such an extract promoted opsonophagocytosis and killing of S. aureus. Immunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue, using an in vivo model of mesh-associated biofilm infection. Furthermore, immunized mice also showed limited organ colonization by bacteria released from the matrix at the dispersive stage of the biofilm cycle. Altogether, these data illustrate the potential of biofilm matrix exoproteins as a promising candidate multivalent vaccine against S. aureus biofilm-associated infections.
| S-EPMC3957983 | biostudies-literature
Project description:Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI), resulting in considerable disability and prolonged treatment. It is known that host leukocyte IL-10 production is required for S. aureus biofilm persistence in PJI. An S. aureus bursa aurealis Tn library consisting of 1,952 non-essential genes was screened for mutants that failed to induce IL-10 in myeloid-derived suppressor cells (MDSCs), which identified a critical role for bacterial lactic acid biosynthesis. We generated an S. aureus ddh/ldh1/ldh2 triple Tn mutant that cannot produce D- or L-lactate. Co-culture of MDSCs or macrophages with ddh/ldh1/ldh2 mutant biofilm produced substantially less IL-10 compared with wild-type S. aureus, which was also observed in a mouse model of PJI and led to reduced biofilm burden. Using MDSCs recovered from the mouse PJI model and in vitro leukocyte-biofilm co-cultures, we show that bacterial-derived lactate inhibits histone deacetylase 11, causing unchecked HDAC6 activity and increased histone 3 acetylation at the Il-10 promoter, resulting in enhanced Il-10 transcription in MDSCs and macrophages. Finally, we show that synovial fluid of patients with PJI contains elevated amounts of D-lactate and IL-10 compared with control subjects, and bacterial lactate increases IL-10 production by human monocyte-derived macrophages.
| S-EPMC7529909 | biostudies-literature
Project description:Tilmicosin is an antimicrobial agent used to treat intramammary infections against Staphylococcus aureus and has clinical anti-inflammatory effects. However, the mechanism by which it modulates the inflammatory process in the mammary gland is unknown. We evaluated the effect of tilmicosin treatment on the modulation of the mammary innate immune response after S. aureus infection and its effect on casein production in mammary epithelial cells. To achieve this goal, we used immortalized mammary epithelial cells (MAC-T), pretreated for 12 h or treated with tilmicosin after infection with S. aureus (ATCC 27543). Our data showed that tilmicosin decreases intracellular infection (P < 0.01) and had a protective effect on MAC-T reducing apoptosis after infection by 80% (P < 0.01). Furthermore, tilmicosin reduced reactive oxygen species (ROS) (P < 0.01), IL-1? (P < 0.01), IL-6 (P < 0.01), and TNF-? (P < 0.05) production. In an attempt to investigate the signaling pathways involved in the immunomodulatory effect of tilmicosin, mitogen-activated protein kinase (MAPK) phosphorylation was measured by fluorescent-activated cell sorting. Pretreatment with tilmicosin increased ERK1/2 (P < 0.05) but decreased P38 phosphorylation (P < 0.01). In addition, the anti-inflammatory effect of tilmicosin helped to preserve casein synthesis in mammary epithelial cells (P < 0.01). This result indicates that tilmicosin could be an effective modulator inflammation in the mammary gland. Through regulation of MAPK phosphorylation, ROS production and pro-inflammatory cytokine secretion tilmicosin can provide protection from cellular damage due to S. aureus infection and help to maintain normal physiological functions of the bovine mammary epithelial cell.
| S-EPMC6358261 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-06-17 | GSE135496 | GEO