@entity1566 ( @entity1566 ) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., @entity39379 ). To determine the in vivo consequences of activating these receptors, ligands specific for @entity8932 or @entity39379 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid macrophage reaction; however, only @entity39379 activation causes macrophage-mediated demyelination and @entity21 . Coactivating @entity8932 reduced the injurious effects of @entity39379 activation. When injected into traumatically injured spinal cord, @entity8932 agonists enhance the endogenous macrophage reaction while conferring neuroprotection. Indeed, dieback of axons was reduced, leading to smaller lesion volumes at the peak of the macrophage response. Moreover, the density of NG2+ cells expressing @entity3111 increased in and near lesions that were enriched with @entity8932 -activated macrophages. In @entity39379 -null mutant (knock-out) @entity19 , dieback of corticospinal tract axons also is reduced after @entity1566 . Collectively, these data support the hypothesis that the ability of macrophages to create an axon growth-permissive microenvironment or cause @entity2359 is receptor dependent and it may be possible to exploit this functional dichotomy to enhance CNS repair. SIGNIFICANCE STATEMENT: There is a growing appreciation that macrophages exert diverse functions in the injured and diseased CNS. Indeed, both macrophage-mediated repair and macrophage-mediated injury occur, and often these effector functions are elicited simultaneously. Understanding the mechanisms governing the reparative and pathological properties of activated macrophages is at the forefront of neuroscience research. In this report, using in vitro and in vivo models of relevance to traumatic @entity1566 ( @entity1566 ), new data indicate that stochastic activation of toll-like and c-type lectin receptors on macrophages causes neuroprotection or @entity2359 , respectively. Although this manuscript focuses on @entity1566 , these two innate immune receptor subtypes are also involved in developmental processes and become activated in macrophages that respond to various @entity16 .

Toll-Like Receptors and XXXX , a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages.

@entity8932 :: ('24088(Tax:10090)', 'Gene') :: ['TLR2'] @entity3111 :: ('22352(Tax:10090)', 'Gene') :: ['vimentin'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity16 :: ('MESH:D009422', 'Disease') :: ['neurological diseases'] @entity39379 :: ('56644(Tax:10090)', 'Gene') :: ['dectin-1'] @entity1566 :: ('MESH:D013119', 'Disease') :: ['Spinal cord injury', 'spinal cord injury', 'SCI'] @entity21 :: ('MESH:D001480', 'Disease') :: ['axonal injury'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity']
@entity39379 :: (56644(Tax:10090),Gene) :: ['Dectin-1']
