The monocytosis during human leptospirosis is associated with modest immune cell activation states

Raffray, L.; Giry, Claude; Vandroux, David; Fayeulle, Stéphanie; Moiton, Marie‐Pierre; Gerber, Anne; Jaffar‐Bandjee, Marie‐Christine; Gasque, Philippe

doi:10.1007/s00430-018-0575-9

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…Monocytes and neutrophils continued to increase while lymphocytes and platelets showed decreasing trends. Although neutrophils and monocytes could recognize leptospires, both have limited capacity to control the pathogen [ 37 – 42 ]. It was reported that pathogenic Leptospira spp.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary haemorrhage as the earliest sign of severe leptospirosis in hamster model challenged with Leptospira interrogans strain HP358

et al. 2022

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Background Severe leptospirosis is challenging as it could evolve rapidly and potentially fatal if appropriate management is not performed. An understanding of the progression and pathophysiology of Leptospira infection is important to determine the early changes that could be potentially used to predict the severe occurrence of leptospirosis. This study aimed to understand the kinetics pathogenesis of Leptospira interrogans strain HP358 in the hamster model and identify the early parameters that could be used as biomarkers to predict severe leptospirosis. Methodology/Principal findings Male Syrian hamsters were infected with Leptospira interrogans strain HP358 and euthanized after 24 hours, 3, 4, 5, 6 and 7 days post-infection. Blood, lungs, liver and kidneys were collected for leptospiral detection, haematology, serum biochemistry and differential expression of pro- and anti-inflammatory markers. Macroscopic and microscopic organ damages were investigated. Leptospira interrogans strain HP358 was highly pathogenic and killed hamsters within 6–7 days post-infection. Pulmonary haemorrhage and blood vessel congestion in organs were noticed as the earliest pathological changes. The damages in organs and changes in biochemistry value were preceded by changes in haematology and immune gene expression. Conclusion/Significance This study deciphered haemorrhage as the earliest manifestation of severe leptospirosis and high levels of IL-1β, CXCL10/IP-10, CCL3/MIP-α, neutrophils and low levels of lymphocytes and platelets serve as a cumulative panel of biomarkers in severe leptospirosis.

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Section: Discussionmentioning

confidence: 99%

Pulmonary haemorrhage as the earliest sign of severe leptospirosis in hamster model challenged with Leptospira interrogans strain HP358

et al. 2022

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“…To our knowledge, there is no human study evidence reported on the downregulation of TLR2 gene during the infection of Leptospira . Previous studies using flowcytometry showed increased TLR2 expression on human polymorphonuclear cells[30] and human neutrophils[31], while one study showed no significant TLR2 expression difference [32] on monocytes of confirmed patients for leptospirosis compared to healthy human samples. With the different types of methodologies used, detection of expression of the human TLR2 gene can be varied.…”

Section: Discussionmentioning

confidence: 99%

The human Toll-like receptor 2 (TLR2) response during pathogenicLeptospirainfection

Kappagoda,

Senevirathne,

Jayasundara

et al. 2023

Preprint

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BackgroundHuman innate immune responses are triggered through the interaction of human pattern recognition receptors and pathogen-associated molecular patterns. The role of toll-like receptor2 (TLR2) in mice innate immune response to leptospirosis is well established, while human studies are limited. The present study aimed to determine the TLR2 response among confirmed cases of leptospirosis.Methodology/Principle findingsThe study has two components. Clinically suspected patients of leptospirosis were confirmed using a previously validated qPCR assay. Total RNA was extracted from patients’ RNA-stabilized whole blood samples. Human TLR2 gene expression (RT-qPCR) analysis was carried out using an exon-exon spanning primer pair, using CFX Maestro™ software. The first set of patient samples was used to calculate the Relative Normalized Expression (ΔΔCq value) of the TLR2 gene in comparison to a healthy control sample and normalized by the reference gene GAPDH (Glyceraldehyde-3-phosphate dehydrogenase). Secondly, recruited patient samples were subjected to TLR2 gene expression analysis and compared to healthy controls and normalized by the reference genes Beta-2-microglobulin(B2M), Hypoxanthine phosphoribosyltransferase 1 (HPRT 1).In the initial cohort of 64 confirmed leptospirosis cases, 18 were selected for human TLR2 gene expression analysis based on criteria of leptospiremia and RNA yield. Within this group, one individual exhibited a down-regulation of TLR2 gene (Expression/ΔΔCq=0.01352), whereas the remaining subjects presented no significant change in gene expression. In a subsequent cohort of 23 confirmed cases, 13 were chosen for similar analysis. Among these, three patients demonstrated down-regulation of TLR2 gene expression, with Expression/ΔΔCq values of 0.86574, 0.47200, and 0.28579, respectively. No TLR2 gene expression was noted in the other patients within this second group.ConclusionsOur investigation into the acute phase of leptospirosis using human clinical samples has revealed a downregulation of TLR2 gene expression. This observation contrasts to the upregulation commonly reported in the majority of in-vitro and in-vivo studies ofLeptospirainfection. These preliminary findings prompt a need for further research to explore the mechanisms underlying TLR2’s role in the pathogenesis of leptospirosis, which may differ in clinical settings compared to laboratory models.Author SummaryThe human immune system employs pattern recognition receptors like toll-like receptor 2 (TLR2) to detect and combat infections such as leptospirosis. While TLR2’s role is well-documented in mice, its function in the human response to leptospirosis remains unclear. Our study evaluated TLR2 activity in patients with confirmed leptospirosis. We conducted a genetic analysis of blood samples from these patients, comparing TLR2 gene activity against healthy individuals, with standard reference genes for accuracy. Contrary to expectations and existing laboratory data, we observed a decrease in TLR2 activity in some patients. This suggests that human TLR2 responses in actual infections may diverge from established laboratory models. These findings indicate a need for further study to understand the human immune response to leptospirosis, which may significantly differ from that observed in controlled experimental settings.

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“…An unusual feature of leptospiral LPS is the activation of host cells via TLR2 instead of TLR4. This factor is observed due to the unique structure of the lipid portion A, present in the LPS molecule (Zhang et al, 2016;Raffray et al, 2019).…”

Section: Etiological Agentmentioning

confidence: 99%

Antibacterial activity of medicinal plants against Leptospira spp.: a literature review

Melo¹

2023

BLACPMA

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Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira that affects animals and humans. This disease is usually treated empirically due to its prevalence in precarious areas without basic sanitation. The use of medicinal plants in less industrialized societies has been one of the main therapeutic resources available. Considering the need touse these natural resources to combat leptospirosis in areas of socioeconomic vulnerability, this study aimed to review the literature on the useof plants with medicinal potential in thetreatment of leptospirosis. The results showed that even though leptospirosis is a common disease in communities lacking basic sanitation and economic development, the number of studies on the use of plants with medicinal potential is scarce. Most of these studies comefrom India, and all plants investigated between 2012 and 2020 had antileptospiral action.

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The monocytosis during human leptospirosis is associated with modest immune cell activation states

Cited by 6 publications

References 43 publications

Pulmonary haemorrhage as the earliest sign of severe leptospirosis in hamster model challenged with Leptospira interrogans strain HP358

Pulmonary haemorrhage as the earliest sign of severe leptospirosis in hamster model challenged with Leptospira interrogans strain HP358

The human Toll-like receptor 2 (TLR2) response during pathogenicLeptospirainfection

Antibacterial activity of medicinal plants against Leptospira spp.: a literature review

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