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2018 ; 9
(ä): 823
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Understanding the Cellular Origin of the Mononuclear Phagocyte System Sheds Light
on the Myeloid Postulate of Immune Paralysis in Sepsis
#MMPMID29740436
Poulin LF
; Lasseaux C
; Chamaillard M
Front Immunol
2018[]; 9
(ä): 823
PMID29740436
show ga
Sepsis, in essence, is a serious clinical condition that can subsequently result
in death as a consequence of a systemic inflammatory response syndrome including
febrile leukopenia, hypotension, and multiple organ failures. To date, such
life-threatening organ dysfunction remains one of the leading causes of death in
intensive care units, with an increasing incidence rate worldwide and
particularly within the rapidly growing senior population. While most of the
clinical trials are aimed at dampening the overwhelming immune response to
infection that spreads through the bloodstream, based on several human
immunological investigations, it is now widely accepted that susceptibility to
nosocomial infections and long-term sepsis mortality involves an
immunosuppressive phase that is characterized by a decrease in some subsets of
dendritic cells (DCs). Only recently substantial advances have been made in terms
of the origin of the mononuclear phagocyte system that is now likely to allow for
a better understanding of how the paralysis of DCs leads to sepsis-related death.
Indeed, the unifying view of each subset of DCs has already improved our
understanding of the pivotal pathways that contribute to the shift in commitment
of their progenitors that originate from the bone marrow. It is quite plausible
that this anomaly in sepsis may occur at the single level of DC-committed
precursors, and elucidating the immunological basis for such a derangement during
the ontogeny of each subset of DCs is now of particular importance for restoring
an adequate cell fate decision to their vulnerable progenitors. Last but not
least, it provides a direct perspective on the development of sophisticated
myelopoiesis-based strategies that are currently being considered for the
treatment of immunosenescence within different tissue microenvironments, such as
the kidney and the spleen.