RESUMO
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)ß clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRß clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes. Our results demonstrate that host exposure to antigen may drive clonal expansion of MAIT cells with increased functional avidity, suggesting a role for specific vaccination strategies to increase the frequency and potency of MAIT cells to optimize effector function.
Assuntos
Proliferação de Células , Células T Invariantes Associadas à Mucosa/imunologia , Febre Paratifoide/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Salmonella paratyphi A/imunologia , Adolescente , Adulto , Linhagem Celular Tumoral , Células Clonais/imunologia , Células Clonais/metabolismo , Células Clonais/microbiologia , Voluntários Saudáveis , Interações Hospedeiro-Patógeno/imunologia , Humanos , Células Jurkat , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/microbiologia , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/metabolismo , Células T Invariantes Associadas à Mucosa/microbiologia , Febre Paratifoide/metabolismo , Febre Paratifoide/microbiologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Salmonella paratyphi A/fisiologia , Adulto JovemRESUMO
The present controlled cross-sectional study aimed to assess elevated values of C-reactive protein (CRP), a positive acute-phase protein, induced by imported infectious diseases (IDs) seen in patients consulting the University of Munich (1999-2015) after being in the tropics/subtropics. The analysis investigated data sets from 11,079 diseased German travelers (cases) returning from Latin America (1,986), Africa (3,387), and Asia (5,706), and from 714 healthy Germans who had not recently traveled (controls). The proportions of elevated values of CRP (> 0.5 mg/dL) were significantly larger among cases (44.3%) than among controls (20.7%). Among cases, this proportion was largest among males (49.2%) in comparison to females (39.9%), among travelers with short travel duration of 1-14 days (49.6%) in comparison to travelers with a travel duration of > 180 days (30.8%), and with travel destination in Africa (47.0%) in comparison to Asia (44.2%) and Latin America (39.9%), among all-inclusive travelers (47.4%) in comparison to business travelers (46.7%) and backpackers (44.1%), and among patients presenting with fever (70.9%) and arthralgia (54.3%). The study identified various imported IDs with significantly larger proportions of elevated values of CRP including viral (cytomegalovirus infection [94.7%], influenza [88.9%], infectious mononucleosis [71.8%]), bacterial (typhoid fever [100%], paratyphoid fever [92.9%], shigellosis [76.8%], rickettsiosis [74.2%], Salmonella enteritis [71.3%], Campylobacter infection [68.7%]), and protozoan (vivax malaria [100%], ovale malaria [100%], falciparum malaria [95.4%], noninvasive Entamoeba infection [65.9%]) IDs. This study demonstrates that elevated values of CRP can be a useful laboratory finding for travelers returning from the tropics/subtropics, as these findings are typically caused mainly by certain imported bacterial IDs, but also by viral and protozoan IDs.
Assuntos
Infecções Bacterianas/metabolismo , Proteína C-Reativa/metabolismo , Doenças Parasitárias/metabolismo , Viagem , Viroses/metabolismo , Adolescente , Adulto , África , Idoso , Idoso de 80 Anos ou mais , Ásia , Infecções por Campylobacter/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Infecções por Citomegalovirus/metabolismo , Disenteria Bacilar/metabolismo , Entamebíase/metabolismo , Enterite/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Alemanha , Humanos , Lactente , Influenza Humana/metabolismo , América Latina , Malária/metabolismo , Masculino , Pessoa de Meia-Idade , Febre Paratifoide/metabolismo , Infecções por Rickettsia/metabolismo , Infecções por Salmonella/metabolismo , Fatores Sexuais , Febre Tifoide/metabolismo , Adulto JovemRESUMO
Salmonella enterica serovar Paratyphi A is a human-specific serovar that, together with Salmonella enterica serovar Typhi and Salmonella enterica serovar Sendai, causes enteric fever. Unlike the nontyphoidal Salmonella enterica serovar Typhimurium, the genomes of S. Typhi and S. Paratyphi A are characterized by inactivation of multiple genes, including in the flagellum-chemotaxis pathway. Here, we explored the motility phenotype of S. Paratyphi A and the role of flagellin in key virulence-associated phenotypes. Motility studies established that the human-adapted typhoidal S. Typhi, S. Paratyphi A, and S. Sendai are all noticeably less motile than S. Typhimurium, and comparative transcriptome sequencing (RNA-Seq) showed that in S. Paratyphi A, the entire motility-chemotaxis regulon is expressed at significantly lowers levels than in S. Typhimurium. Nevertheless, S. Paratyphi A, like S. Typhimurium, requires a functional flagellum for epithelial cell invasion and macrophage uptake, probably in a motility-independent mechanism. In contrast, flagella were found to be dispensable for host cell adhesion. Moreover, we demonstrate that in S. Paratyphi A, but not in S. Typhimurium, the lack of flagellin results in increased transcription of the flagellar and the Salmonella pathogenicity island 1 (SPI-1) regulons in a FliZ-dependent manner and in oversecretion of SPI-1 effectors via type three secretion system 1. Collectively, these results suggest a novel regulatory linkage between flagellin and SPI-1 in S. Paratyphi A that does not occur in S. Typhimurium and demonstrate curious distinctions in motility and the expression of the flagellum-chemotaxis regulon between these clinically relevant pathogens.
Assuntos
Flagelina/metabolismo , Febre Paratifoide/metabolismo , Salmonella paratyphi A/patogenicidade , Proteínas de Bactérias/biossíntese , Western Blotting , Células CACO-2 , Humanos , Espectrometria de Massas , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Enteric fever, caused by Salmonella enterica, remains an unresolved public health problem in India and antimicrobial therapy is the main mode of treatment. The objective of this study was to characterize the Salmonella enterica isolates from Kolkata with respect to their antimicrobial resistance (AMR), virulence profiles and molecular subtypes. Salmonella enterica blood isolates were collected from clinically suspected enteric fever patients attending various hospitals in Kolkata, India from January 2009 to June 2013 and were tested for AMR profiles by standard protocols; for resistance gene transfer by conjugation; for resistance and virulence genes profiles by PCR; and for molecular subtypes by Pulsed Field Gel Electrophoresis (PFGE). A total of 77 Salmonella enterica serovar Typhi (S. Typhi) and 25 Salmonella enterica serovar Paratyphi A (S. Paratyphi A) from Kolkata were included in this study. Although multidrug resistance (resistance to chloramphenicol, ampicillin, co-trimoxazole) was decreasing in S. Typhi (18.2%) and absent in S. Paratyphi A, increased resistance to fluoroquinolone, the current drug of choice, caused growing concern for typhoid treatment. A single, non-conjugative non-IncHI1 plasmid of 180 kb was found in 71.4% multidrug resistant (MDR) S. Typhi; the remaining 28.6% isolates were without plasmid. Various AMR markers (blaTEM-1, catA, sul1, sul2, dfrA15, strA-strB) and class 1 integron with dfrA7 gene were detected in MDR S. Typhi by PCR and sequencing. Most of the study isolates were likely to be virulent due to the presence of virulence markers. Major diversity was not noticed among S. Typhi and S. Paratyphi A from Kolkata by PFGE. The observed association between AMR profiles and S. Typhi pulsotypes might be useful in controlling the spread of the organism by appropriate intervention. The study reiterated the importance of continuous monitoring of AMR and molecular subtypes of Salmonella isolates from endemic regions for better understanding of the disease epidemiology.
Assuntos
Proteínas de Bactérias , Farmacorresistência Bacteriana , Febre Paratifoide , Salmonella paratyphi A , Salmonella typhi , Febre Tifoide , Fatores de Virulência , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Masculino , Febre Paratifoide/epidemiologia , Febre Paratifoide/genética , Febre Paratifoide/metabolismo , Febre Paratifoide/microbiologia , Salmonella paratyphi A/genética , Salmonella paratyphi A/isolamento & purificação , Salmonella paratyphi A/metabolismo , Salmonella paratyphi A/patogenicidade , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Salmonella typhi/metabolismo , Salmonella typhi/patogenicidade , Febre Tifoide/epidemiologia , Febre Tifoide/genética , Febre Tifoide/metabolismo , Febre Tifoide/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
ClyASTy and ClyASPaA are closely related pore-forming cytolysins of Salmonella enterica serovars Typhi and Paratyphi A whose expression is strongly repressed under standard in vitro growth conditions. We show here that human infections by these pathogens cause a specific antibody response to ClyA, indicating effective toxin production during infection.
Assuntos
Citotoxinas/biossíntese , Febre Paratifoide/metabolismo , Salmonella paratyphi A/fisiologia , Salmonella typhi/fisiologia , Febre Tifoide/metabolismo , Citotoxinas/análise , Citotoxinas/sangue , Citotoxinas/imunologia , Humanos , Febre Paratifoide/sangue , Febre Paratifoide/imunologia , Salmonella paratyphi A/imunologia , Salmonella typhi/imunologia , Especificidade da Espécie , Febre Tifoide/sangue , Febre Tifoide/imunologiaAssuntos
Aminoácidos/metabolismo , Doenças Transmissíveis/metabolismo , Corticosteroides/metabolismo , Aminoácidos/sangue , Animais , Bacillus subtilis , Infecções Bacterianas/metabolismo , Infecções por Coxsackievirus/metabolismo , Cães , Cobaias , Humanos , Absorção Intestinal , Meningite/metabolismo , Camundongos , Febre Paratifoide/metabolismo , Ratos , Esquistossomose/metabolismo , Estações do Ano , Especificidade da Espécie , Infecções Estafilocócicas/metabolismo , Febre Tifoide/metabolismoRESUMO
Twenty-eight patients with typhoid fever and one patient with paratyphoid fever were subjected to intestinal function tests (faecal fat and D-xylose) and jejunal biopsy soon after recovery from the acute phase of the disease in order to assess the residual functional and morphological status of the small bowel. The results indicate that almost 50% (14/29) initially had defective D-xylose absorption which recovered rapidly. No patient had steatorrhoea. Jejunal biopsies of eight patients out of 22 showed increased chronic cell infiltration; there was, however, no specific lesion. It appears that intestinal injury following salmonellosis results only in mild functional derangement of the bowel which recovers rapidly.