MyD88-deficient mice exhibit decreased parasite-induced immune responses but reduced disease severity in a murine model of neurocysticercosis.
The symptomatic phase of neurocysticercosis (NCC), a parasitic disease of the central nervous system (CNS) in humans, is characterized by inflammatory responses leading to neuropathology and, in some cases, death. In an animal model of NCC in which mice were intracranially inoculated with the parasite Mesocestoides corti, the infection in mice lacking the myeloid differentiation primary response gene 88 (MyD88(-/-)) resulted in decreased disease severity and improved survival compared with that in wild-type (WT) mice. The CNS of MyD88(-/-) mice was more quiescent, with decreased microgliosis and tissue damage. These mice exhibited substantially reduced primary and secondary microglial nodule formations and lacked severe astrogliotic reactions, which were seen in WT mice. Significantly reduced numbers of CD11b(+) myeloid cells, alphabeta T cells, gammadelta T cells, and B cells were present in the brains of MyD88(-/-) mice in comparison with those of WT mice. This decrease in cellular infiltration correlated with a decrease in blood-brain barrier permeability, as measured by reduced fibrinogen extravasation. Comparisons of cytokine expression indicated a significant decrease in the CNS levels of several inflammatory mediators, such as tumor necrosis factor alpha, gamma interferon, CCL2, and interleukin-6, during the course of infection in MyD88(-/-) mice. Collectively, these findings suggest that MyD88 plays a prominent role in the development of the hyperinflammatory response, which in turn contributes to neuropathology and disease severity in NCC.
Mishra
Bibhuti B
BB
Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, Texas 78249-1644, USA.
Gundra
Uma Mahesh
UM
Wong
Kondi
K
Teale
Judy M
JM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D005260:Female; D008645:Mesocestoides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000276:immunology*; D020019:Neurocysticercosis / Q000276:immunology* / Q000473:pathology*; D012720:Severity of Illness Index; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88