High leptospiremia is associated with low gamma–delta T cell counts

Raffray, L.; Giry, Claude; Thirapathi, Yoga; Binois, François; Moiton, Marie‐Pierre; Lagrange-Xélot, Marie; Ferrándiz, Daniel Álvarez; Jaffar‐Bandjee, Marie‐Christine; Gasque, Philippe

doi:10.1016/j.micinf.2015.04.001

Cited by 5 publications

(6 citation statements)

References 24 publications

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“…Plasma bacterial load is established from the plasma PCR values (n = 12) and using the log-transformed standard curve as described [27]. Horizontal bars indicate the median.…”

Section: Resultsmentioning

confidence: 99%

“…Leptospires in plasma or urine were detected by quantitative real-time PCR (qPCR) using the Light cycler LC480 system (Roche), and TaqMan® Universal PCR Mastermix with primers and probe specific for 23S rRNA gene of Leptospira as detailed before [27]. For quantification of bacterial burden in plasma by PCR, serial dilutions of genomic DNA extracts from L .…”

Section: Methodsmentioning

confidence: 99%

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Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

et al. 2016

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It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.

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“…Plasma bacterial load is established from the plasma PCR values (n = 12) and using the log-transformed standard curve as described [27]. Horizontal bars indicate the median.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

et al. 2016

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“…Hamsters and humans, which exhibit acute disease, express high levels of pro-inflammatory cytokines IL-6 and TNFα in infected tissues or from PBMC (Matsui et al, 2011 ; Volz et al, 2015 ). Increased levels of IL-10, while also highly expressed in infected hamsters, were associated with milder disease in humans (Raffray et al, 2015 ). Humans with higher bacterial burdens had decreased numbers of circulating ⋎δ-T cells (Raffray et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness

Nally

Wilson-Welder

Hornsby

et al. 2018

Front. Cell. Infect. Microbiol.

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Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection, excrete large numbers of organisms in their urine. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host's cellular immune response that facilitates persistent renal colonization. To address this deficiency, we established and applied an immunocompetent inbred rat model of persistent renal colonization; leptospires were detected in urine of experimentally infected rats by 3 weeks post-infection and remained positive until 8 weeks post-infection. However, there was little, if any, evidence of inflammation in colonized renal tubules. At 8 weeks post-infection, a robust antibody response was detected against lipopolysaccharide and protein outer membrane (OM) components. Purified B and T cells derived from the spleen of infected and non-infected rats proliferated in response to stimulation with 0.5 μg of OM fractions of Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells, compared to 25% in non-infected controls. However, analysis of gene expression did not determine which immunoregulatory pathways were activated. Lymphocytes purified from the lymph node draining the site of colonization, the renal lymph node, also showed an increase in percentage of proliferating B and T cells. However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T cells. These results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs. systemic, immune responses during renal colonization infection. The use of inbred immunocompetent rats provides a novel tool to further elucidate those pathophysiological pathways that facilitate the unique biological equilibrium observed in reservoir hosts of leptospirosis.

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“…Leptospires in plasma or urine were detected by quantitative real-time PCR (qPCR) using the Light cycler LC480 ® system (Roche), and TaqMan ® Universal PCR Mastermix with primers and probe specific for 23S rRNA gene of Leptospira as detailed before [21]. For quantification of bacterial burden in plasma by PCR, serial dilutions of genomic DNA extracts from L .…”

Section: Methodsmentioning

confidence: 99%

Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis

et al. 2017

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Leptospirosis is a multisystemic zoonotic disease with infiltration of visceral organs by Leptospira. The capacity of the vascular endothelium to grant immune cell recruitment and activation in target organs during the disease course remains poorly characterized. We ascertained the levels of expression of several soluble cell adhesion molecules (CAM) notably expressed by endothelial cells in human leptospirosis. We prospectively enrolled 20 hospitalized patients and compared them to 10 healthy controls. Disease severity was defined by one or more organ failures, or death. Plasmatic concentrations of soluble CAM were assessed by multiplex bead assay at the time of patient presentation (M0) and 1 month after hospital discharge. The levels of soluble E-selectin (sCD62E) and soluble intercellular adhesion molecule 1 (sICAM-1, sCD53) were significantly increased in patients compared to controls (p<0.0001) and at 1 month (p<0.0001) with median values at 978 ng/ml (interquartile ranges 787–1164; sCD62E) and 1021 ng/ml (690–1428; sCD53). At M0, Soluble P-selectin level (sCD62P) was found to be decreased with levels at 60 ng/ml (0–631) versus 711 ng/ml (343–1113) for healthy controls (p<0.05). Levels of sICAM-3 (sCD50), sVCAM-1 (vascular cell adhesion molecule, sCD106) and sPECAM-1 (platelet endothelial cell adhesion molecule, sCD31) were not different from healthy subjects at M0. This study shows that two adhesion molecules, shed as soluble forms, are elevated during the acute phase of leptospirosis: E-selectin and s-ICAM1. These molecules may interfere with the process of immune cell recruitment to clear Leptospira at tissue levels.

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High leptospiremia is associated with low gamma–delta T cell counts

Cited by 5 publications

References 24 publications

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness

Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis

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