title: A specific Toll-like receptor profile on T lymphocytes and values of monocytes correlate with bacterial, fungal, and cytomegalovirus infections in the early period of allogeneic stem cell transplantation.
abstract: BACKGROUND
  Bacterial, fungal, and viral infections often affect non-relapse mortality after allogeneic stem cell transplantation (alloSCT). Recovery from infections depends on a balanced integration between innate and adaptive immune responses. In this complex interplay, a key role is played by Toll-like receptors (TLRs), which are sensors of pathogen-associated molecular patterns. To our knowledge, no previous study deals with both expression and function of all human TLRs together, in relation to infections in the setting of alloSCT.
  
  
  METHODS
  We prospectively evaluated 9 TLRs by flow cytometry on T lymphocytes and monocytes of 35 patients in relation to infectious events from day +30 to day +120. Tumor necrois factor-alpha, interleukin-4, interferon-gamma, and monocyte chemoattractant protein-1 induction upon TLR activation was assessed by enzyme-linked immunosorbent assay on cell supernatants.
  
  
  RESULTS
  In multivariate Cox regression analysis, levels of TLR-9 expression on T lymphocytes (P = 0.01) and values of natural killer cells (P = 0.01) correlated negatively with bacterial infections, whereas cytomegalovirus (CMV) infection resulted as a positive predictor. We observed a trend for negative correlation between TLR-7 levels on T lymphocytes and fungal infections (P = 0.07). Values of monocytes were negatively associated with CMV infection (P = 0.03), whereas levels of TLR-5 on T lymphocytes were positive predictors (P = 0.01). Age (P = 0.03) and bacterial infections (P = 0.006) negatively influenced overall survival. Monocyte values were positive predictors of survival (P = 0.003).
  
  
  CONCLUSIONS
  Bacterial, fungal, and CMV infections were associated with a different expression of some TLRs on T lymphocytes. The protective role of TLR-7 and TLR-9 seemed dominant over other TLRs involved in recognizing fungi and bacteria. We also observed an atypical involvement of TLR-5 in CMV infection. The dominant and atypical role of some TLRs could depend on their pleiotropic functions and the changing inflammatory environment of transplanted patients. A specific TLR profile and an adequate count of monocytes could improve survival, promoting an effective control of infections, and balanced immune responses. If our findings will be confirmed by further studies, these immunological variables could be useful as parameters to predict susceptibility to infections.
authors.affiliation: Hematology, Stem Cell Transplantation Unit, University of Brescia, Brescia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Skert
authors.forename: M
authors.initials: M
authors.lastname: Fogli
authors.forename: E
authors.initials: E
authors.lastname: Garaffa
authors.forename: S
authors.initials: S
authors.lastname: Perucca
authors.forename: S
authors.initials: S
authors.lastname: Fiorentini
authors.forename: V
authors.initials: V
authors.lastname: Cancelli
authors.forename: A
authors.initials: A
authors.lastname: Turra
authors.forename: R
authors.initials: R
authors.lastname: Ribolla
authors.forename: C
authors.initials: C
authors.lastname: Filì
authors.forename: M
authors.initials: M
authors.lastname: Malagola
authors.forename: C
authors.initials: C
authors.lastname: Bergonzi
authors.forename: F
authors.initials: F
authors.lastname: Cattina
authors.forename: S
authors.initials: S
authors.lastname: Bernardi
authors.forename: A
authors.initials: A
authors.lastname: Caruso
authors.forename: A
authors.initials: A
authors.lastname: Di Palma
authors.forename: D
authors.initials: D
authors.lastname: Russo
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001424:Bacterial Infections / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry* / Q000276:immunology; D009181:Mycoses / Q000276:immunology; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D013997:Time Factors; D051198:Toll-Like Receptor 5 / Q000032:analysis; D051199:Toll-Like Receptor 7 / Q000032:analysis; D051217:Toll-Like Receptor 9 / Q000032:analysis; D051193:Toll-Like Receptors / Q000819:agonists / Q000032:analysis*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D018932:Chemokine CCL2; C495346:TLR5 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Toll-like receptors; infections; lymphocytes; monocytes; stem cell transplantation