The monocytosis during human leptospirosis is associated with modest immune cell activation states
- 46 Downloads
Leptospirosis is a life-threatening zoonotic disease and it has been hypothesized that the innate immune system fails to control the infection through ill-characterized mechanisms. The aim of this observational study was to better evaluate the activation processes of monocytes at the early stage of the disease. Blood samples were taken from healthy donors (n = 37) and patients hospitalized for either non-severe (n = 25) or severe (n = 32) leptospirosis. Monocyte cell counts and phenotypes were assessed by flow cytometry. We analysed the expression of several cell activation markers: CD14, CD16, HLA-DR, CD69, TLR2, TLR4, CD11b and CD11c. Although monocyte values at admittance were not significantly different from controls, patients experienced significant monocytosis at 1.33 × 109/L (p < 0.0001 compared to controls: 0.56 × 109/L) during their hospital stay. This monocytosis observed during hospital stay was correlated to several surrogate markers of organ injury. Non-classical (CD14−CD16+) and intermediate (CD14+CD16+) monocyte subsets increased compared to controls (p < 0.05). Accordingly, classical monocyte subset (CD14+CD16−) showed decreased percentages (p < 0.0001). Levels of several cell surface activation molecules were decreased: HLA-DR involved in MHC class II antigen presentation, integrins CD11b and CD11c implicated in phagocytosis and cell recruitment (p < 0.0001). None of these parameters had a prognostic value. Results from this study showed that during acute human leptospirosis, patients experienced monocytosis with a switch toward an inflammation-related phenotype contrasted by low expression levels of markers implicated in monocyte function.
KeywordsLeptospirosis Innate immunity Monocytes HLA-DR Phagocytosis
The authors thank the practitioners implicated in the patients’ care as well as the members of the microbiology laboratory of St Denis, La Réunion, for their help in patients’ recruitment. We also thank Alexander Greenshields for critical appraisal of the manuscript.
The authors work is funded by the research unit PIMIT (processus infectieux en milieu insulaire tropical) and the CHU (centre hospitalo-universaire) de la Réunion. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors have no competing interest to declare.
This study was approved by the local human ethic committee of tertiary teaching Hospital ‘CHU de La Réunion’ (protocol number R15018) and conducted according to the principles expressed in the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study.
- 17.Raffray L, Giry C, Vandroux D et al (2016) Major neutrophilia observed in acute phase of human leptospirosis is not associated with increased expression of granulocyte cell activation markers. PLoS One 11:e0165716. https://doi.org/10.1371/journal.pone.0165716 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Bellomo R, Ronco C, Kellum JA et al (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute dialysis quality initiative (ADQI) Group. Crit Care 8:R204–212. https://doi.org/10.1186/cc2872 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Bone RC, Balk RA, Cerra FB et al (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM consensus conference committee. Am Coll Chest Phys Soc Critical Care Med Chest 101:1644–1655Google Scholar
- 28.Craig SB, Graham GC, Burns M-A et al (2009) Haematological and clinical-chemistry markers in patients presenting with leptospirosis: a comparison of the findings from uncomplicated cases with those seen in the severe disease. Ann Trop Med Parasitol 103:333–341. https://doi.org/10.1179/136485909X435058 CrossRefPubMedGoogle Scholar
- 39.Brunialti MKC, Martins PS, Barbosa de Carvalho H et al (2006) TLR2, TLR4, CD14, CD11B, and CD11C expressions on monocytes surface and cytokine production in patients with sepsis, severe sepsis, and septic shock. Shock 25:351–357. https://doi.org/10.1097/01.shk.0000217815.57727.29 CrossRefPubMedGoogle Scholar