RESUMO
Introduction: The CC chemokine ligand 18 (CCL18) is a chemokine highly expressed in chronic inflammation in humans. Recent observations of elevated CCL18 plasma levels in patients with acute cardiovascular syndromes prompted an investigation into the role of CCL18 in the pathogenesis of human and mouse atherosclerosis. Methods and results: CCL18 was profoundly upregulated in ruptured human atherosclerotic plaque, particularly within macrophages. Repeated administration of CCL18 in Western-type diet-fed ApoE -/- mice or PCSK9mut-overexpressing wild type (WT) mice led to increased plaque burden, enriched in CD3+ T cells. In subsequent experimental and molecular modeling studies, we identified CCR6 as a functional receptor mediating CCL18 chemotaxis, intracellular Ca2+ flux, and downstream signaling in human Jurkat and mouse T cells. CCL18 failed to induce these effects in vitro in murine spleen T cells with CCR6 deficiency. The ability of CCR6 to act as CCL18 receptor was confirmed in vivo in an inflammation model, where subcutaneous CCL18 injection induced profound focal skin inflammation in WT but not in CCR6-/- mice. This inflammation featured edema and marked infiltration of various leukocyte subsets, including T cells with a Th17 signature, supporting CCR6's role as a Th17 chemotactic receptor. Notably, focal overexpression of CCL18 in plaques was associated with an increased presence of CCR6+ (T) cells. Discussion: Our studies are the first to identify the CCL18/CCR6 axis as a regulator of immune responses in advanced murine and human atherosclerosis.
Assuntos
Aterosclerose , Quimiocinas CC , Receptores CCR6 , Animais , Humanos , Aterosclerose/imunologia , Aterosclerose/metabolismo , Camundongos , Receptores CCR6/metabolismo , Receptores CCR6/genética , Quimiocinas CC/metabolismo , Quimiocinas CC/genética , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Células Jurkat , Placa Aterosclerótica/imunologia , Camundongos Knockout , Masculino , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Feminino , Camundongos Knockout para ApoERESUMO
BACKGROUND: Klebsiella pneumoniae infections have become a major cause of hospital acquired infection worldwide with the increased rate of acquisition of resistance to antibiotics. Carbapenem resistance mainly among Gram negative is an ongoing problem which causes serious outbreaks dramatically limiting treatment options. This prospective cross-sectional study was designed to detect blaKPC gene from carbapenem resistant K. pneumoniae. MATERIALS AND METHODS: A totally of 1118 different clinical specimens were screened and confirmed for KPC producing K. pneumoniae phenotypically using Meropenem (10 µg) disc. The blaKPC gene was amplified from the isolates of K. pneumoniae to detect the presence of this gene. RESULT: Of the total samples processed, 18.6% (n = 36) were K. pneumoniae and among 36 K. pneumoniae, 61.1% (n = 22/36) were meropenem resistant. This study demonstrated the higher level of MDR 91.7% (n = 33) and KPC production 47.2% (n = 17) among K. pneumoniae isolates. The blaKPC gene was detected in 8.3% (n = 3) of meropenem resistant isolates. CONCLUSION: Since the study demonstrates the higher level of MDR and KPC producing K. pneumoniae isolates that has challenged the use of antimicrobial agents, continuous microbiology, and molecular surveillance to assist early detection and minimize the further dissemination of blaKPC should be initiated. We anticipate that the findings of this study will be useful in understanding the prevalence of KPC-producing K. pneumoniae in Nepal.
Assuntos
Antibacterianos , Proteínas de Bactérias , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária , beta-Lactamases , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/enzimologia , beta-Lactamases/genética , Humanos , Nepal/epidemiologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Proteínas de Bactérias/genética , Estudos Transversais , Estudos Prospectivos , Antibacterianos/farmacologia , Meropeném/farmacologia , Masculino , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Idoso , AdolescenteRESUMO
Objective: To investigate the molecular epidemiology and antimicrobial resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) among healthcare workers and patients. Methods: MRSA isolates were recovered from nasal swabs collected at a tertiary care hospital of Nepal and confirmed on the basis of Gram staining, conventional biochemical tests, and PCR amplification of mecA gene. PCRs were also used for detection of the different resistance genes and staphylococcal cassette chromosome (SCC) mec types. Antibiotic susceptibility patterns of isolates were assessed by disc diffusion method and minimum inhibitory concentrations were determined by E-test. Results: A total of 29 MRSA were isolated from 536 nasal swabs (5.4%) of health care workers and patients at a tertiary care hospital in Nepal. All isolates were susceptible to amikacin, gentamicin, vancomycin (minimal inhibitory concentrations1024μg/mL). Fourteen isolates were found harboring the mupA gene and one isolate was found carrying the novel mupB gene. High prevalence (68%) of SCCmec I type was found, followed by SCCmec V (13%) and SCCmec III (3%) among all the MRSA isolates. Conclusions: We found the emergence of SCCmec type Ⅰ with high-level mupirocin resistance among MRSA in Nepal. Data also suggest that MRSA SCCmec type V strain has spread from the community to the hospital.