Macrophage migration inhibitory factor (MIF) deficiency enhances immune response to Nippostrongylus brasiliensis

Autor: Janet V. Cross, Rebecca K. Martin, Daniel H. Conrad, Sheela R. Damle
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
medicine.medical_treatment
animal diseases
Immunology
chemical and pharmacologic phenomena
GATA3 Transcription Factor
Article
Parasite Load
Type 2 immune response
03 medical and health sciences
Mice
Immune system
Th2 Cells
Antigen
Isothiocyanates
medicine
otorhinolaryngologic diseases
Immunology and Allergy
Animals
Nippostrongylus
Nippostrongylus brasiliensis
Macrophage Migration-Inhibitory Factors
Cells
Cultured
Strongylida Infections
Mice
Knockout
Mice
Inbred BALB C
Interleukin-13
biology
Macrophages
Immunity
respiratory system
biology.organism_classification
biological factors
3. Good health
Intramolecular Oxidoreductases
Mice
Inbred C57BL
030104 developmental biology
Cytokine
Antigens
Helminth
Sulfoxides
Interleukin 13
Macrophage migration inhibitory factor
Female
Zdroj: Mucosal immunology
ISSN: 1935-3456
1933-0219
Popis: Infections with helminth parasites are endemic in the developing world and are a target for intervention with new therapies. Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic effects in inflammation and immune responses. We investigated the role of MIF in a naturally cleared model of helminth infection in rodents, Nippostrongylus brasiliensis. At day 7 postinfection, MIF-deficient (MIF-/-) mice had reduced parasite burden and mounted an enhanced type 2 immune response (Th2), including increased Gata3 expression and interleukin-13 (IL-13) production in the mesenteric lymph nodes (MLNs). Bone marrow reconstitution demonstrated that MIF produced from hematopoietic cells was crucial and Rag1-/- reconstitution provided direct evidence that MIF-/- CD4+ T cells were responsible for the augmented parasite clearance. MIF-/- CD4+ T cells produced less IL-6 postinfection, which correlated with enhanced Th2 responses. MIF-/- CD4+ T cells exhibited lower nuclear factor-κB activation, potentially explaining the reduction in IL-6. Finally, we demonstrated enhanced clearance of the parasite and Th2 response in wild-type mice treated with the MIF tautomerase inhibitor, sulforaphane, a compound found naturally found in cruciferous vegetables. These results are the first to describe the importance of the tautomerase enzyme activity in MIF function in N. brasiliensis infection.
Databáze: OpenAIRE
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