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Pathogen-Specific Immune Fingerprints during Acute Infection: The Diagnostic Potential of Human γδ T-Cells.

Eberl M, Friberg IM, Liuzzi AR, Morgan MP, Topley N - Front Immunol (2014)

View Article: PubMed Central - PubMed

Affiliation: Cardiff Institute of Infection and Immunity, School of Medicine, Cardiff University , Cardiff , UK.

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The fact that the prevalence of resistance appears to correlate directly with antibiotic consumption across different countries argues in favor of the immediate effectiveness of such tightly controlled programs... As highlighted in a recent Outlook issue in Nature, “the potential to save lives with faster and more targeted diagnoses, decrease unnecessary and often incorrect prescriptions, and even help identify early on where bacterial resistance could occur, will have a drastic effect on the way patients are treated”... Approaches based on the detection of microbial nucleic acids, cell wall constituents, or other unique features of distinct pathogens by PCR, chromatography, or mass spectrometry certainly complement culture-based tests and speed up microbial identification, yet they require considerable resources and may not be applicable to primary care or home settings... Moreover, they do not provide information about the pathogenicity of the identified species and its interaction with the host... Of note, neither microbiological nor molecular methods discriminate between pathogens causing disease, asymptomatic carriage, and sample contaminants, and thus even positive test results require extensive interpretation by the treating physician... As a result, neither the direct identification of the causative pathogen nor the measurement of currently used biomarkers of inflammation is sufficiently accurate or rapid for a reliable point-of-care diagnosis of acute microbial infection... The immune system appears to have originated as a set of effector cells having multiple distinct receptors that discriminate self from infectious non-self by recognition of patterns found exclusively on microorganisms. – Charles A... Vγ9/Vδ2 T-cells represent a unique subpopulation of human T-cells that appears to have a particularly crucial role in contributing to immune fingerprints of diagnostic relevance... This is due to their exquisite responsiveness to the microbial isoprenoid precursor (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) that is produced by the majority of Gram-negative pathogens and a large proportion of Gram-positive species such as Clostridium difficile, Listeria monocytogenes, and Mycobacterium tuberculosis, while it is not found in other bacteria including staphylococci and streptococci as well as fungi... Bacterial extracts prepared from HMB-PP producing species typically activate Vγ9/Vδ2 T-cells much stronger than extracts prepared from HMB-PP deficient micro-organisms, and peripheral and/or local Vγ9/Vδ2 T-cell levels are often elevated in patients infected with defined HMB-PP producing pathogens... Our own data demonstrate that even in heterogeneous patient cohorts infected with a whole spectrum of diverse bacteria, differences in Vγ9/Vδ2 T-cell frequencies between patients with microbiologically confirmed infections caused by HMB-PP producing and HMB-PP deficient species remain apparent... Most importantly, studies in patients with acute peritonitis suggest that a diagnostic test measuring local Vγ9/Vδ2 T-cells on the first day of presentation with acute symptoms may not only indicate the presence of Gram-negative (predominantly HMB-PP producing) bacteria but also identify patients at an increased risk of inflammation-related downstream complications... Pathogen-specific immune fingerprints that discriminate between certain subgroups of patients (e.g., with Gram-negative vs... It remains to be investigated how much these findings on diagnostic immune fingerprints in peritoneal dialysis patients can be extended to other local or systemic scenarios to diagnose infections at the point of care, and whether they can also be applied to monitoring the course of the disease and the response to treatment.

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Related in: MedlinePlus

Local immune fingerprints in peritoneal dialysis patients on the day of presentation with acute peritonitis. Shown are cellular and humoral biomarkers that are associated with the presence of Gram-positive or Gram-negative bacteria and that may be exploited for novel diagnostic tests (34).
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Figure 1: Local immune fingerprints in peritoneal dialysis patients on the day of presentation with acute peritonitis. Shown are cellular and humoral biomarkers that are associated with the presence of Gram-positive or Gram-negative bacteria and that may be exploited for novel diagnostic tests (34).

Mentions: The exquisite responsiveness of Vγ9/Vδ2 T-cells and other unconventional T-cells to microbial metabolites shared by certain pathogens but not by others identifies these cell types as key constituent of diagnostically relevant immune fingerprints at the point of care. This is especially the case when Vγ9/Vδ2 T-cell levels are assessed locally and when they are combined with other powerful discriminators such as peritoneal proportions of neutrophils, monocytes, and CD4+ T-cells in the inflammatory infiltrate as well as intraperitoneal concentrations of certain soluble immune mediators (34) (Figure 1). Such a combination with further parameters provides additional information as to the precise nature of the causative pathogen, for instance to distinguish between immune responses induced by Gram-negative (LPS producing) and Gram-positive (LPS deficient) bacteria, and is also likely to help increase sensitivity owing to the age and gender-dependent variability of Vγ9/Vδ2 T-cell levels (55). Pathogen-specific immune fingerprints that discriminate between certain subgroups of patients (e.g., with Gram-negative vs. Gram-positive bacterial infections) can be determined within hours of presentation with acute symptoms, long before traditional culture results become available, and by guiding early patient management and optimizing targeted treatment will contribute to improving outcomes and advancing antibiotic stewardship. It remains to be investigated how much these findings on diagnostic immune fingerprints in peritoneal dialysis patients can be extended to other local or systemic scenarios to diagnose infections at the point of care, and whether they can also be applied to monitoring the course of the disease and the response to treatment.


Pathogen-Specific Immune Fingerprints during Acute Infection: The Diagnostic Potential of Human γδ T-Cells.

Eberl M, Friberg IM, Liuzzi AR, Morgan MP, Topley N - Front Immunol (2014)

Local immune fingerprints in peritoneal dialysis patients on the day of presentation with acute peritonitis. Shown are cellular and humoral biomarkers that are associated with the presence of Gram-positive or Gram-negative bacteria and that may be exploited for novel diagnostic tests (34).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230182&req=5

Figure 1: Local immune fingerprints in peritoneal dialysis patients on the day of presentation with acute peritonitis. Shown are cellular and humoral biomarkers that are associated with the presence of Gram-positive or Gram-negative bacteria and that may be exploited for novel diagnostic tests (34).
Mentions: The exquisite responsiveness of Vγ9/Vδ2 T-cells and other unconventional T-cells to microbial metabolites shared by certain pathogens but not by others identifies these cell types as key constituent of diagnostically relevant immune fingerprints at the point of care. This is especially the case when Vγ9/Vδ2 T-cell levels are assessed locally and when they are combined with other powerful discriminators such as peritoneal proportions of neutrophils, monocytes, and CD4+ T-cells in the inflammatory infiltrate as well as intraperitoneal concentrations of certain soluble immune mediators (34) (Figure 1). Such a combination with further parameters provides additional information as to the precise nature of the causative pathogen, for instance to distinguish between immune responses induced by Gram-negative (LPS producing) and Gram-positive (LPS deficient) bacteria, and is also likely to help increase sensitivity owing to the age and gender-dependent variability of Vγ9/Vδ2 T-cell levels (55). Pathogen-specific immune fingerprints that discriminate between certain subgroups of patients (e.g., with Gram-negative vs. Gram-positive bacterial infections) can be determined within hours of presentation with acute symptoms, long before traditional culture results become available, and by guiding early patient management and optimizing targeted treatment will contribute to improving outcomes and advancing antibiotic stewardship. It remains to be investigated how much these findings on diagnostic immune fingerprints in peritoneal dialysis patients can be extended to other local or systemic scenarios to diagnose infections at the point of care, and whether they can also be applied to monitoring the course of the disease and the response to treatment.

View Article: PubMed Central - PubMed

Affiliation: Cardiff Institute of Infection and Immunity, School of Medicine, Cardiff University , Cardiff , UK.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The fact that the prevalence of resistance appears to correlate directly with antibiotic consumption across different countries argues in favor of the immediate effectiveness of such tightly controlled programs... As highlighted in a recent Outlook issue in Nature, “the potential to save lives with faster and more targeted diagnoses, decrease unnecessary and often incorrect prescriptions, and even help identify early on where bacterial resistance could occur, will have a drastic effect on the way patients are treated”... Approaches based on the detection of microbial nucleic acids, cell wall constituents, or other unique features of distinct pathogens by PCR, chromatography, or mass spectrometry certainly complement culture-based tests and speed up microbial identification, yet they require considerable resources and may not be applicable to primary care or home settings... Moreover, they do not provide information about the pathogenicity of the identified species and its interaction with the host... Of note, neither microbiological nor molecular methods discriminate between pathogens causing disease, asymptomatic carriage, and sample contaminants, and thus even positive test results require extensive interpretation by the treating physician... As a result, neither the direct identification of the causative pathogen nor the measurement of currently used biomarkers of inflammation is sufficiently accurate or rapid for a reliable point-of-care diagnosis of acute microbial infection... The immune system appears to have originated as a set of effector cells having multiple distinct receptors that discriminate self from infectious non-self by recognition of patterns found exclusively on microorganisms. – Charles A... Vγ9/Vδ2 T-cells represent a unique subpopulation of human T-cells that appears to have a particularly crucial role in contributing to immune fingerprints of diagnostic relevance... This is due to their exquisite responsiveness to the microbial isoprenoid precursor (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) that is produced by the majority of Gram-negative pathogens and a large proportion of Gram-positive species such as Clostridium difficile, Listeria monocytogenes, and Mycobacterium tuberculosis, while it is not found in other bacteria including staphylococci and streptococci as well as fungi... Bacterial extracts prepared from HMB-PP producing species typically activate Vγ9/Vδ2 T-cells much stronger than extracts prepared from HMB-PP deficient micro-organisms, and peripheral and/or local Vγ9/Vδ2 T-cell levels are often elevated in patients infected with defined HMB-PP producing pathogens... Our own data demonstrate that even in heterogeneous patient cohorts infected with a whole spectrum of diverse bacteria, differences in Vγ9/Vδ2 T-cell frequencies between patients with microbiologically confirmed infections caused by HMB-PP producing and HMB-PP deficient species remain apparent... Most importantly, studies in patients with acute peritonitis suggest that a diagnostic test measuring local Vγ9/Vδ2 T-cells on the first day of presentation with acute symptoms may not only indicate the presence of Gram-negative (predominantly HMB-PP producing) bacteria but also identify patients at an increased risk of inflammation-related downstream complications... Pathogen-specific immune fingerprints that discriminate between certain subgroups of patients (e.g., with Gram-negative vs... It remains to be investigated how much these findings on diagnostic immune fingerprints in peritoneal dialysis patients can be extended to other local or systemic scenarios to diagnose infections at the point of care, and whether they can also be applied to monitoring the course of the disease and the response to treatment.

No MeSH data available.


Related in: MedlinePlus