Distinctive homing profile of pathogen-specific activated lymphocytes in human urinary tract infection

Palkola, Nina V.; Arvilommi, Heikki; Kantele, Jussi M.

doi:10.1016/j.clim.2008.05.003

Cited by 16 publications

(33 citation statements)

References 52 publications

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“…Mucosal vaccination has been shown to elicit both strong humoral and cellular responses on mucous membranes as well as systemically. In this study, we chose intranasal immunization, since it induces immune responses at all relevant entry sites of ExPEC infections (20,26). Here we used the adjuvant cholera toxin, which is highly efficient on mucosal surfaces in mice.…”

Section: Discussionmentioning

confidence: 99%

A Multiepitope Subunit Vaccine Conveys Protection against Extraintestinal PathogenicEscherichia coliin Mice

et al. 2010

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Infections due to extraintestinal pathogenic Escherichia coli (ExPEC) are common in humans and animals and include urinary tract infections (from uropathogenic E. coli [UPEC]), septicemia, and wound infections. These infections result in significant morbidity and mortality and in high health care costs. In view of the increasing number of ExPEC infections and the ever-growing antibiotic resistance capability of ExPEC isolates, preventive measures such as an effective vaccine against ExPEC are desirable. An ExPEC vaccine may be cost-effective for select patient groups. Previous vaccine candidates consisted of single target proteins or whole ExPEC cells. Here we describe a subunit vaccine against ExPEC which is based on immunodominant epitopes of the virulence-associated ExPEC proteins FyuA, IroN, ChuA, IreA, Iha, and Usp. Using a novel approach of computer-aided design, two completely artificial genes were created, both encoding eight peptide domains derived from these ExPEC proteins. The recombinant expression of these two genes resulted in a protein vaccine directed against ExPEC but not against commensal E. coli of the gut flora. In mice, the vaccine was highly immunogenic, eliciting both strong humoral and cellular immune responses. Nasal application resulted in high secretory immunoglobulin A (sIgA) production, which was detectable on the mucosal surface of the urogenital tract. Finally, it conveyed protection, as shown by a significant reduction of bacterial load in a mouse model of ExPEC peritonitis. This study provides evidence that a novel vaccine design encompassing distinct epitopes of virulenceassociated ExPEC proteins may represent a means for providing a protective and pathogen-specific vaccine.

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Section: Discussionmentioning

confidence: 99%

A Multiepitope Subunit Vaccine Conveys Protection against Extraintestinal PathogenicEscherichia coliin Mice

et al. 2010

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“…This has biological plausibility, since P fimbriated E. coli has increased uroepithelial binding and are associated with increased virulence in UTI (79). Following activation in the urinary tract, antigen-specific ASCs express a unique set of homing receptors that may induce migration to regional lymph nodes (34). …”

Section: Asc Kineticsmentioning

confidence: 99%

The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications

Carter

Mitchell

Sauteur³

et al. 2017

Front. Immunol.

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Despite the availability of advances in molecular diagnostic testing for infectious disease, there is still a need for tools that advance clinical care and public health. Current methods focus on pathogen detection with unprecedented precision, but often lack specificity. In contrast, the host immune response is highly specific for the infecting pathogen. Serological studies are rarely helpful in clinical settings, as they require acute and convalescent antibody testing. However, the B cell response is much more rapid and short-lived, making it an optimal target for determining disease aetiology in patients with infections. The performance of tests that aim to detect circulating antigen-specific antibody-secreting cells (ASCs) has previously been unclear. Test performance is reliant on detecting the presence of ASCs in the peripheral blood. As such, the kinetics of the ASC response to infection, the antigen specificity of the ASC response, and the methods of ASC detection are all critical. In this review, we summarize previous studies that have used techniques to enumerate ASCs during infection. We describe the emergence, peak, and waning of these cells in peripheral blood during infection with a number of bacterial and viral pathogens, as well as malaria infection. We find that the timing of antigen-specific ASC appearance and disappearance is highly conserved across pathogens, with a peak response between day 7 and day 8 of illness and largely absent following day 14 since onset of symptoms. Data show a sensitivity of ~90% and specificity >80% for pathogen detection using ASC-based methods. Overall, the summarised work indicates that ASC-based methods may be very sensitive and highly specific for determining the etiology of infection and have some advantages over current methods. Important areas of research remain, including more accurate definition of the timing of the ASC response to infection, the biological mechanisms underlying variability in its magnitude and the evolution and the B cell receptor in response to immune challenge. Nonetheless, there is potential of the ASC response to infection to be exploited as the basis for novel diagnostic tests to inform clinical care and public health priorities.

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“…All of these studies are done in bacterial UTI models, but Epa proteins of C. glabrata have also been demonstrated to mediate adherence and could potentially be blocked by Abs (73). Another focus in research of bacterial UTIs has been the identification and quantification of Absecreting cells, including their lymphocyte homing receptors, in the blood of patients with pyelonephritis as an indicator of local immune response (131,132). In candiduria the serological response has been investigated, but clear correlations with invasive disease were not established (262).…”

Section: Immune Responses To Candiduriamentioning

confidence: 99%

Candida Infections of the Genitourinary Tract

2010

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SUMMARYAll humans are colonized withCandidaspecies, mostlyCandida albicans, yet some develop diseases due toCandida, among which genitourinary manifestations are extremely common. The forms of genitourinary candidiasis are distinct from each other and affect different populations. While vulvovaginal candidiasis affects mostly healthy women, candiduria occurs typically in elderly, hospitalized, or immunocompromised patients and in neonates. Despite its high incidence and clinical relevance, genitourinary candidiasis is understudied, and therefore, important questions about pathogenesis and treatment guidelines remain to be resolved. In this review, we summarize the current knowledge about genitourinary candidiasis.

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Distinctive homing profile of pathogen-specific activated lymphocytes in human urinary tract infection

Cited by 16 publications

References 52 publications

A Multiepitope Subunit Vaccine Conveys Protection against Extraintestinal PathogenicEscherichia coliin Mice

A Multiepitope Subunit Vaccine Conveys Protection against Extraintestinal PathogenicEscherichia coliin Mice

The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications

Candida Infections of the Genitourinary Tract

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