Medical Microbiology and Immunology

, Volume 208, Issue 5, pp 667–678 | Cite as

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

  • Loic RaffrayEmail author
  • Claude Giry
  • David Vandroux
  • Stéphanie Fayeulle
  • Marie-Pierre Moiton
  • Anne Gerber
  • Marie-Christine Jaffar-Bandjee
  • Philippe Gasque
Original Investigation


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.


Leptospirosis 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.

Ethical approval

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.

Supplementary material

430_2018_575_MOESM1_ESM.tiff (316 kb)
Supplementary Fig. 1: Evolution of monocyte cell counts during hospitalization and convalescent phase for 10 leptospirosis patients. Caption: Paired values of monocytes for leptospirosis cases during hospitalization (admittance and maximal value) and 1 month after discharge (M1). Comparisons with non-parametric Wilcoxon paired test. ** indicates P value inferior to 0.01, respectively. (TIFF 315 KB)
430_2018_575_MOESM2_ESM.tiff (290 kb)
Supplementary Fig. 2: Higher bacteraemia in severe leptospirosis cases. Caption: Plasmatic Leptospira load is established from the 50 patients with positive RT-qPCR in blood and using the log-transformed standard curve. Horizontal bars indicate the median and IQR ranges. Comparison with non-parametric Mann-Whitney test. ** indicates P value inferior to 0.01. (TIFF 289 KB)
430_2018_575_MOESM3_ESM.tiff (668 kb)
Supplementary Fig. 3: Higher levels of cell surface expression of CD69 on monocytes in severe cases of leptospirosis Caption: comparison of selected cell surface markers among healthy donors and leptospirosis patients according to disease severity. Horizontal bars indicate the median and IQR ranges for mean fluorescence intensity (MFI). Comparison with non-parametric Mann-Whitney test. **, **** indicate P values inferior to 0.01 and 0.0001, respectively. (TIFF 667 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Université de La Réunion, CNRS 9192, INSERM U1187, IRD 249, UMR PIMIT, CHU de La Réunion, Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Plateforme Technologique CYROISainte-ClotildeFrance
  2. 2.Internal Medicine UnitCHU La Réunion site Félix GuyonSt DenisFrance
  3. 3.CNR arboviroses, CHU La Réunion site Félix GuyonSt DenisFrance
  4. 4.Microbiology/Virology LaboratoryCHU La Réunion site Félix GuyonSt DenisFrance
  5. 5.Intensive Care UnitCHU La Réunion site Félix GuyonSt DenisFrance
  6. 6.Internal Medicine UnitGHER HospitalSt BenoitFrance
  7. 7.Infectious and Tropical Diseases UnitCHU La Réunion site Félix GuyonSt DenisFrance
  8. 8.Biology laboratory, Immunology sector, LICE-OICHU La Réunion site Félix GuyonSt DenisFrance

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