Lack of galectin-3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection.
Galectin-3 is a beta-galactoside-binding lectin implicated in the fine-tuning of innate immunity. Rhodococcus equi, a facultative intracellular bacterium of macrophages, causes severe granulomatous bronchopneumonia in young horses and immunocompromised humans. The aim of this study is to investigate the role of galectin-3 in the innate resistance mechanism against R. equi infection. The bacterial challenge of galectin-3-deficient mice (gal3-/-) and their wild-type counterpart (gal3+/+) revealed that the LD50 for the gal3(-/-) mice was about seven times higher than that for the gal3+/+ mice. When challenged with a sublethal dose, gal3(-/-) mice showed lower bacteria counts and higher production of IL-12 and IFN-gamma production, besides exhibiting a delayed although increased inflammatory reaction. Gal3(-/-) macrophages exhibited a decreased frequency of bacterial replication and survival, and higher transcript levels of IL-1beta, IL-6, IL-10, TLR2 and MyD88. R. equi-infected gal3+/+ macrophages showed decreased expression of TLR2, whereas R. equi-infected gal3(-/-) macrophages showed enhanced expression of this receptor. Furthermore, galectin-3 deficiency in macrophages may be responsible for the higher IL-1beta serum levels detected in infected gal3(-/-) mice. Therefore galectin-3 may exert a regulatory role in innate immunity by diminishing IL-1beta production and thus affecting resistance to R. equi infection.
Ferraz
Luciana C
LC
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
Bernardes
Emerson S
ES
Oliveira
Aline F
AF
Ruas
Luciana P
LP
Fermino
Marise L
ML
Soares
Sandro G
SG
Loyola
Adriano M
AM
Oliver
Constance
C
Jamur
Maria C
MC
Hsu
Daniel K
DK
Liu
Fu-Tong
FT
Chammas
Roger
R
Roque-Barreira
Maria-Cristina
MC
D000193:Actinomycetales Infections / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D037502:Galectin 3 / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016929:Rhodococcus equi / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D037502:Galectin 3; D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D018664:Interleukin-12