Increased percentages of T helper cells producing IL-17 and monocytes expressing markers of alternative activation in patients with sepsis.
BACKGROUND
A shift from Th1 to Th2 as well as an increase in Treg CD4+T cell subsets has been reported in septic patients (SP). Furthermore, these patients display modulation of monocyte function, with reduced production of pro-inflammatory cytokines upon LPS stimulus, which resembles the phenotype of alternatively activated macrophages. In this study, we evaluated the percentages of T cells differentiated into Th1, Th17 and Treg subsets, as well as the percentage of monocytes expressing markers of alternatively activated monocytes/macrophages (AAM) in SP.


RESULTS
Peripheral blood mononuclear cells (PBMC) were obtained from 32 healthy volunteers (HV) and from SP at admission (D0, n = 67) and after 7 days of therapy (D7, n = 33). Th1 and Th17 (CD3+CD8-) lymphocytes were identified by the intracellular detection of IFN-γ and IL-17, respectively, spontaneously and after PMA/Io stimulation, and Treg cells were identified by Foxp3+CD127- expression. Monocytes were evaluated for CD206 and CD163 expression. Absolute numbers of CD4+T lymphocytes were measured in whole blood samples by flow cytometry. The Mann-Whitney or Wilcoxon test was applied, as appropriate. The percentage of Th1 cells was lower in SP than in HV at admission after PMA/Io stimulation, whereas the percentage of Th17 cells was higher. In patients' follow-up samples, a higher percentage of Th1 cells and a lower percentage of Th17 cells were observed on D7 compared with the D0 samples. Treg cells remained unchanged. Septic patients showed a markedly increased proportion of monocytes expressing CD163 and CD206.


CONCLUSIONS
Upon in vitro stimulus, the percentage of T helper lymphocytes producing IL-17 was higher in SP than in HV at admission, and the percentage producing IFN-γ was lower, a pattern that was reversed during follow-up. The increased expression of CD163 and CD206 indicates that monocytes may acquire the AAM phenotype during sepsis.
Division of Infectious Diseases, Department of Medicine, Hospital Sao Paulo, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
Milena Karina Colo
MK
Brunialti
Michelle Carolina
MC
Santos
Otelo
O
Rigato
Flavia Ribeiro
FR
Machado
Eliezer
E
Silva
Reinaldo
R
Salomao
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D018805:Sepsis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D020381:Interleukin-17; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface