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Abstract
Indirect acute lung injury (ALI, not caused by a direct insult to the lung) represents
the first organ dysfunction in trauma patients, with nonpulmonary sepsis being the
most common cause of indirect ALI. Dendritic cells (DCs) are thought to participate
in a number of inflammatory lung diseases; however, their role in indirect ALI is
currently not established. Using a clinically relevant model of indirect ALI induced
in mice by hemorrhagic shock followed 24 hours later by polymicrobial septic challenge,
we report that mature DC numbers were markedly increased in the lung during indirect
ALI. DC depletion induced a significant increase in indirect ALI severity, which was
associated with enhanced lung and plasma proinflammatory cytokine concentration and
recruitment of proinflammatory CD115(+) monocytes in response to increased lung monocyte
chemotactic protein-1 production. Among the different DC subpopulations, plasmacytoid
DCs, which were induced and activated in the lung during indirect ALI, were responsible
for this effect because their specific depletion reproduced the observations made
in DC-depleted mice. As the recruitment of monocytes to the lung plays a central deleterious
role in the pathophysiology of indirect ALI, our data therefore position plasmacytoid
DCs as important regulators of acute lung inflammation.