@article{fdi:010052898,
  title = {{H}uman fatal {Z}aire {E}bola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis},
  author = {{W}auquier, {N}. and {B}ecquart, {P}ierre and {P}adilla, {C}. and {B}aize, {S}. and {L}eroy, {E}ric},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {E}bolavirus species {Z}aire ({ZEBOV}) causes highly lethal hemorrhagic fever, resulting in the death of 90% of patients within days. {M}ost information on immune responses to {ZEBOV} comes from in vitro studies and animal models. {T}he paucity of data on human immune responses to this virus is mainly due to the fact that most outbreaks occur in remote areas. {P}ublished studies in this setting, based on small numbers of samples and limited panels of immunological markers, have given somewhat different results. {M}ethodology/{P}rincipal {F}indings: {H}ere, we studied a unique collection of 56 blood samples from 42 nonsurvivors and 14 survivors, obtained during the five outbreaks that occurred between 1996 and 2003 in {G}abon and {R}epublic of {C}ongo. {U}sing {L}uminex technology, we assayed 50 cytokines in all 56 samples and performed phenotypic analyses by flow cytometry. {W}e found that fatal outcome was associated with hypersecretion of numerous proinflammatory cytokines ({IL}-1b, {IL}-1{RA}, {IL}-6, {IL}-8, {IL}-15 and {IL}-16), chemokines and growth factors ({MIP}-1 alpha, {MIP}-1 beta, {MCP}-1, {M}-{CSF}, {MIF}, {IP}-10, {GRO}-alpha and eotaxin). {I}nterestingly, no increase of {IFN} alpha 2 was detected in patients. {F}urthermore, nonsurvivors were also characterized by very low levels of circulating cytokines produced by {T} lymphocytes ({IL}-2, {IL}-3, {IL}-4, {IL}-5, {IL}-9, {IL}-13) and by a significant drop of {CD}3+{CD}4+ and {CD}3+{CD}8+ peripheral cells as well as a high increase in {CD}95 expression on {T} lymphocytes. {C}onclusions/{S}ignificance: {T}his work, the largest study to be conducted to date in humans, showed that fatal outcome is associated with aberrant innate immune responses and with global suppression of adaptive immunity. {T}he innate immune reaction was characterized by a "cytokine storm," with hypersecretion of numerous proinflammatory cytokines, chemokines and growth factors, and by the noteworthy absence of antiviral {IFN} alpha 2. {I}mmunosuppression was characterized by very low levels of circulating cytokines produced by {T} lymphocytes and by massive loss of peripheral {CD}4 and {CD}8 lymphocytes, probably through {F}as/{F}as{L}-mediated apoptosis.},
  keywords = {{GABON}},
  booktitle = {},
  journal = {{P}los {N}eglected {T}ropical {D}iseases},
  volume = {4},
  numero = {10},
  pages = {e837},
  ISSN = {1935-2727},
  year = {2010},
  DOI = {10.1371/journal.pntd.0000837},
  URL = {https://www.documentation.ird.fr/hor/fdi:010052898},
}