Previous studies suggest that the complement system can contribute to limiting pneumococcal outgrowth within the CNS. In this study, we evaluated the role of the complement system in the activation of the innate immune response and the development of the prognosis-relevant @entity1504 in a @entity19 model of @entity2506 . Thereby, we used @entity19 deficient in @entity13697 , lacking only the classical pathway, and C3, lacking all three complement activation pathways. At 24 h after intracisternal @entity281 , bacterial titers in the CNS were almost 12- and 20-fold higher in @entity13697 - and @entity18195 - @entity19 , respectively, than in wild-type @entity19 . Mean CSF leukocyte counts were reduced by 47 and 73% in @entity13697 - and @entity18195 - @entity19 , respectively. Intrathecal reconstitution with wild-type serum in @entity18195 @entity19 restored both the ability of @entity19 to combat @entity7706 of the CSF and the ability of leukocytes to egress into the CSF. The altered recruitment of leukocytes into the CSF of @entity18195 @entity19 was paralleled by a strong reduction of the brain expression of cytokines and chemokines. The dampened immune response in @entity18195 @entity19 was accompanied by a reduction of @entity693 -induced @entity1504 , but, surprisingly, also with a worsening of short-term outcome. The latter seems to be due to more severe @entity2259 (12- and 120-fold higher in @entity13697 - and @entity18195 - @entity19 , respectively) and, consecutively, more severe systemic complications. Thus, our study demonstrated for the first time that the complement system plays an integral role in mounting the intense host immune response to @entity328 @entity281 of the CNS.

Complement XXXX and C3 are critical for the innate immune response to @entity328 in the central nervous system.

@entity13697 :: ('12259(Tax:10090)', 'Gene') :: ['C1q'] @entity7706 :: ('MESH:D011008', 'Disease') :: ['pneumococcal infection'] @entity19 :: ('10090', 'Species') :: ['mice', 'murine'] @entity2506 :: ('MESH:D008586', 'Disease') :: ['pneumococcal meningitis'] @entity1504 :: ('MESH:D002561', 'Disease') :: ['intracranial complications'] @entity18195 :: ('MESH:C565169', 'Disease') :: ['C3-deficient'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity693 :: ('MESH:D008581', 'Disease') :: ['meningitis'] @entity328 :: ('1313', 'Species') :: ['Streptococcus pneumoniae'] @entity2259 :: ('MESH:D016470', 'Disease') :: ['bacteremia']
@entity13697 :: (12259(Tax:10090),Gene) :: ['C1q']
