FGF8 protects against polymicrobial sepsis by enhancing the host's anti-infective immunity.

Background: Sepsis is characterized by a life-threatening syndrome caused by an unbalanced host response to infection. Fibroblast Growth Factor 8 (FGF8) has been newly identified to play important roles in inflammation and innate immunity, but its role in host response to sepsis is undefined.

Methods: A cecal ligation and puncture (CLP) -induced mouse sepsis model was established to evaluate the immunomodulatory function of FGF8 during sepsis.

Immunization with recombinant PgdA protects mice against lung invasion.

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of pneumoniae in the lungs without affecting nasopharyngeal carriage.

Transcriptional regulation of TacL-mediated lipoteichoic acids biosynthesis by ComE during competence impacts pneumococcal transformation.

Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation.

Bone morphogenetic protein 9 is a candidate prognostic biomarker and host-directed therapy target for sepsis.

Defining next-generation immune therapeutics for the treatment of sepsis will involve biomarker-based therapeutic decision-making. Bone morphogenetic protein 9 (BMP9) is a cytokine in the transforming growth factor-β superfamily. Here, circulating BMP9 concentrations were quantified in two independent cohorts of patients with sepsis.

Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.

Candidemia is a severe disease with high mortality in both intensive care unit (ICU) and non-ICU settings. Considering that progranulin (PGRN) is a potential therapeutic target for the candidemia caused by Candida albicans, we determined the serum level of PGRN after candidemia and evaluated its association with mortality. A retrospective discovery cohort (62 patients) and a validation cohort (70 patients) were enrolled.

The preprogrammed anti-inflammatory phenotypes of CD11c macrophages by Streptococcus pneumoniae aminopeptidase N safeguard from allergic asthma.

Background: Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined.

Methods: BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen.

Detoxified pneumolysin derivative ΔA146Ply inhibits triple- negative breast cancer metastasis mainly via mannose receptor-mediated autophagy inhibition.

The detoxified pneumolysin derivative ΔA146Ply has been proven to have a direct anti-triple negative breast cancer effect by our group, but its work model remains unclear. In this study, we focused on its ability to inhibit triple-negative breast cancer metastasis. We found that ΔA146Ply suppressed the migration and invasion of triple-negative breast cancer cells by activating mannose receptor and toll-like receptor 4.

The Streptococcus virulence protein PepO triggers anti-tumor immune responses by reprograming tumor-associated macrophages in a mouse triple negative breast cancer model.

Background: The efficacy of current surgery and chemotherapy for triple negative breast cancer (TNBC) is limited due to heterogenous and immunosuppressive tumor microenvironment (TME). Tumor associated macrophages (TAMs), which are regarded as an M2 tumor-promoting phenotype, are crucial in the development of the immunosuppressive TME. Targeting TAM reprograming is a promising strategy in anti-tumor therapy since reprogramming techniques provide the opportunity to actively enhance the antitumor immunological activity of TAM in addition to eliminating their tumor-supportive roles, which is rarely applied in TNBC clinically.

ΔA146Ply-HA stem protein immunization protects mice against influenza A virus infection and co-infection with Streptococcus pneumoniae.

Influenza virus (IV) is a common pathogen affecting the upper respiratory tract, that causes various diseases. Secondary bacterial pneumonia is a common complication and a major cause of death in influenza patients. Streptococcus pneumoniae (S.

Identification of cis-acting elements upstream of regR gene in streptococcus pneumoniae.

The identification and characterization of functional cis-acting elements is of fundamental importance for comprehending the regulatory mechanisms of gene transcription and bacterial pathogenesis. The transcription factor RegR has been demonstrated to control both competence and virulence in Streptococcus pneumoniae. Despite the clear contribution of RegR to these pathways, the mechanisms underlying its transcriptional regulation remain poorly understood.

(Competence) Operon Is Regulated by CcpA in Streptococcus pneumoniae D39.

Natural transformation plays an important role in the formation of drug-resistant bacteria. Exploring the regulatory mechanism of natural transformation can aid the discovery of new antibacterial targets and reduce the emergence of drug-resistant bacteria. Competence is a prerequisite of natural transformation in Streptococcus pneumoniae, in which operon is the core regulator of competence.

CCL3 aggravates intestinal damage in NEC by promoting macrophage chemotaxis and M1 macrophage polarization.

Background: NEC is a life-threatening gastrointestinal disease in neonates, the pathogenesis of which remains poorly understood.

Methods: CCL3 levels in intestinal tissue of mice were measured and analyzed. HE staining was used to assess pathological changes in intestinal tissue.

Glucose levels affect MgaSpn regulation on the virulence and adaptability of Streptococcus pneumoniae.

Streptococcus pneumoniae can regulate virulence gene expression by sensing environmental changes, which is key to its pathogenicity. The global transcription regulator MgaSpn of Streptococcus pneumoniae regulates virulence genes expression by directly binding to the promoter regions, but its role in response to different environments remains unclear. In this study, we found that glucose levels could affect phosphocholine content, which was mediated by MgaSpn.

rM2e-ΔPly protein immunization induces protection against influenza viruses and its co-infection with Streptococcus pneumoniae in mice.

Current seasonal influenza A virus (IAV) vaccines only protect against specific virus and require annual reconstitution to accommodate the viral mutations. A universal influenza vaccination that protects against all IAV strains is urgently needed. The influenza matrix protein 2 ectodomain (M2e) is a potential universal IAV vaccine candidate, but it has a low immunogenicity.

Prokineticin 2 promotes macrophages-mediated antibacterial host defense against bacterial pneumonia.

Objectives: Bacterial pneumonia is a common serious infectious disease with high morbidity and mortality. Prokineticin 2 (PK2) has recently been identified as a novel immunomodulator in a variety of diseases; however, its role in bacterial pneumonia remains unclear.

Methods: The levels of PK2 were measured and analyzed in patients with pneumonia and healthy controls.

Progranulin aggravates lethal Candida albicans sepsis by regulating inflammatory response and antifungal immunity.

Candida albicans is the most frequent pathogen of fungal sepsis associated with substantial mortality in critically ill patients and those who are immunocompromised. Identification of novel immune-based therapeutic targets from a better understanding of its molecular pathogenesis is required. Here, we reported that the production of progranulin (PGRN) levels was significantly increased in mice after invasive C.

CD5L attenuates allergic airway inflammation by expanding CD11c alveolar macrophages and inhibiting NLRP3 inflammasome activation via HDAC2.

Allergic asthma is an airway inflammatory disease dominated by type 2 immune responses and there is currently no curative therapy for asthma. CD5-like antigen (CD5L) has been known to be involved in a variety of inflammatory diseases. However, the role of CD5L in allergic asthma remains unclear.

Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling.

Leukemia is caused by the malignant clonal expansion of hematopoietic stem cells, and in adults, the most common type of leukemia is acute myeloid leukemia (AML). Autophagy inhibitors are often used in preclinical and clinical models in leukemia therapy. However, clinically available autophagy inhibitors and their efficacy are very limited.

Novel Therapeutic Targeting of CCL3-CCR4 Axis Mediated Apoptotic Intesitnal Injury in Necrotizing Enterocolitis.

Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal-related death, while the etiology and pathogenesis are poorly understood.

Methods: The levels of CCL3 in intestinal tissue from modeling mice and patients were measured and analyzed. HE staining, TUNEL, Annexin and FCM were used to assess pathological changes and apoptosis in intestinal tissue and epithelial cells.

IL-6 Prevents Lung Macrophage Death and Lung Inflammation Injury by Inhibiting GSDME- and GSDMD-Mediated Pyroptosis during Pneumococcal Pneumosepsis.

Streptococcus pneumoniae is a leading bacterial cause of a wide range of infections, and pneumococcal pneumosepsis causes high mortality in hosts infected with antibiotic-resistant strains and those who cannot resolve ongoing inflammation. The factors which influence the development and outcome of pneumosepsis are currently unclear. IL-6 is critical for maintaining immune homeostasis, and we determined that this cytokine is also essential for resisting pneumosepsis, as it inhibits macrophage pyroptosis and pyroptosis-related inflammation injury in the lung.

IL-4 plays an essential role in DnaJ-ΔA146Ply-mediated immunoprotection against Streptococcus pneumoniae in mice.

The fusion protein DnaJ-ΔA146Ply is protective against pneumococcal infections in mice. However, we found that immunized IL-4 mice showed significant lower survival rates and higher bacterial loads than did wild-type (WT) mice after being challenged. We explored the role of IL-4 in the protective immunity conferred by DnaJ-ΔA146Ply.

IL-27 as a potential biomarker for distinguishing between necrotising enterocolitis and highly suspected early-onset food protein-induced enterocolitis syndrome with abdominal gas signs.

Background: The initial clinical manifestations and abdominal imaging findings of neonates with necrotising enterocolitis (NEC) and food protein-induced enterocolitis syndrome (FPIES) are sometimes similar; however, their prognosis and therapies are different. We aimed to evaluate the utility of interleukin (IL)-27 as a differentiation marker between NEC and highly suspected early onset (HSEO)-FPIES.

Methods: All samples used in this study were obtained from the neonatal diagnosis centre of Children's Hospital of Chongqing Medical University.

Identifying Prokineticin2 as a Novel Immunomodulatory Factor in Diagnosis and Treatment of Sepsis.

Objectives: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown.

Mga is a negative regulator of capsule and phosphorylcholine biosynthesis and influences the virulence of D39.

Global transcriptional regulators are prevalent in gram-positive pathogens. The transcriptional regulators of the Mga/AtxA family regulate target gene expression by directly binding to the promoter regions, that results in the coordinated expression of virulence factors. The gene of strain D39 encodes Mga, which shares sequence similarity with global transcriptional regulators of the Mga/AtxA family.