RESUMO
We tested the possibility to map loci affecting the acute inflammatory response (AIR) in an (AIRmax AIRmin) F2 intercrossmouse population derived from non-inbred parents, by association analysis in the absence of pedigree information. Using 1064 autosomal single nucleotide polymorphisms (SNPs), we clustered the intercross population into 12 groups of genetically related individuals. Association analysis adjusted for genetic clusters allowed to identify two loci, inflammatory response modulator 1 (Irm1) on chromosome 7 previously detected by genetic linkage analysis in the F2 mice, and a new locus onchromosome 5 (Irm2), linked to the number of infiltrating cells in subcutaneous inflammatory exudates (Irm1: P»6.3 10 7; Irm2: P»8.2 10 5) and interleukin 1 beta (IL-1b) production (Irm1: P»1.9 10 16; Irm2: P»1.1 10 6). Use of a polygenic model based on additive effects of the rare alleles of 15 or 18 SNPs associated at suggestive genome-wide statistical threshold(Po3.4 10 3) with the number of infiltrating cells or IL-1b production, respectively, allowed prediction of the inflammatory response of progenitor AIR mice. Our findings suggest the usefulness of association analysis in combination with genetic clustering to map loci affecting complex phenotypes in non-inbred animal species.
Assuntos
Camundongos , Análise por Conglomerados , Hereditariedade/genética , Hereditariedade/imunologia , Ligação Genética/genética , Reação de Fase Aguda/imunologia , Análise Citogenética/métodos , Polimorfismo de Nucleotídeo Único/imunologiaRESUMO
Control of Haemonchus placei, one of the most important cattle nematodes in Brazil, relies on the use of anthelmintics. However, there is a need for integrated control, which includes active immunization. The aim of this work was to assess the protection afforded to calves by immunization with adult H. placei extracts against a high-dose challenge infection, a condition frequently found in the tropics. Holstein calves aged 8-10 months were immunized four times with intestinal extracts (Group D) or with a Triton X-100-soluble fraction of adult H. placei (Group A), challenge-infected with 120,000 infective larvae and sacrificed 40 days later. Immunized animals had higher IgG titers than the controls against tested fractions after the 2nd immunization, peaking after the 4th. Sera from both immunized groups recognized bands of similar apparent mass in both antigenic preparations, some of which were similar in molecular weight to Haemonchus contortus antigens with known protective effect to sheep. Egg counts were 49% and 57% lower in Groups A and D than in controls, respectively. High levels of protection were observed in two of the four calves in Group D, as evidenced by very low worm numbers recovered at necropsy, absence of eggs in the uteri of the recovered females and reduced worm length. Group D animals also showed milder signs of anemia than the other infected animals. Results demonstrate that protection against homologous high-dose challenge can be achieved by immunizing calves with H. placei gut antigens.
Assuntos
Antígenos de Helmintos/imunologia , Doenças dos Bovinos/prevenção & controle , Hemoncose/veterinária , Haemonchus/imunologia , Imunização/veterinária , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/administração & dosagem , Bovinos , Doenças dos Bovinos/parasitologia , Feminino , Hemoncose/prevenção & controle , Haemonchus/química , Imunoglobulina G/sangue , Intestinos/química , Masculino , Membranas/química , Contagem de Ovos de Parasitas/veterinária , Distribuição Aleatória , Fatores de TempoRESUMO
Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax(RR), AIRmax(SS), AIRmin(RR) and AIRmin(SS) lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax(RR) mice reached 29%, whereas PIA incidence in AIRmax(SS) mice was 70% by day 180. AIRmin(RR) mice were resistant, whereas 13.3% of AIRmin(SS) mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1(SS) mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.
Assuntos
Artrite Reumatoide/genética , Proteínas de Transporte de Cátions/genética , Predisposição Genética para Doença , Inflamação/genética , Terpenos , Alelos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/imunologia , Cromossomos de Mamíferos , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Frequência do Gene , Inflamação/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Repetições de Microssatélites , Locos de Características Quantitativas , Baço/citologiaRESUMO
Mice obtained by bidirectional selective breeding for high (HIII) or low (LIII) antibody (Ab) production are resistant or extremely susceptible to pristane-induced arthritis (PIA), respectively. Several quantitative trait loci regulating Ab production (Ab QTL) have been mapped in these lines, which were used to investigate the influence of these Ab QTL in PIA. Parental HIII and LIII mice and their F1 and F2 intercrosses were injected twice with pristane, and arthritis was observed for 200 days. In LIII mice PIA was more severe and incidence was 100% at day 105, while F1 and F2 mice showed intermediate values. HIII mice were totally resistant. Microsatellite polymorphisms of Ab QTL were analysed and D3Mit100 alleles cosegregated significantly with PIA incidence, severity and onset in F2 intercross mice, while the other four markers showed suggestive values. Results indicate colocalization of QTL for Ab production and PIA susceptibility. Moreover, the different cytokine and IgG isotype profiles observed in HIII and LIII lines after PIA induction are useful to candidate genes endowed with the regulation of the Ab production and arthritis phenotypes.
Assuntos
Artrite Experimental/genética , Artrite Experimental/imunologia , Autoanticorpos/biossíntese , Predisposição Genética para Doença , Locos de Características Quantitativas , Animais , Artrite Experimental/induzido quimicamente , Cruzamentos Genéticos , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Repetições de Microssatélites , Terpenos/toxicidadeRESUMO
In vitro tests were carried out to assess the activity of 26 Brazilian isolates of predatory fungi of the genus Arthrobotrys on a free-living nematode (Panagrellus sp.) and on infective larvae of Haemonchus placei, a parasitic gastrointestinal nematode of cattle. The results showed that the free-living nematode Panagrellus sp. was the most preyed upon, compared to H. placei, for all the fungal treatments. Also, variable predatory capacity was observed for different fungal isolates belonging to the same genus when applied to different nematode species
Assuntos
Animais , Bovinos , Técnicas In Vitro , Fungos Mitospóricos/patogenicidade , Nematoides/microbiologia , Brasil , Haemonchus/microbiologia , Fungos Mitospóricos/isolamento & purificação , Comportamento PredatórioRESUMO
In vitro tests were carried out to assess the activity of 26 Brazilian isolates of predatory fungi of the genus Arthrobotrys on a free-living nematode (Panagrellus sp.) and on infective larvae of Haemonchus placei, a parasitic gastrointestinal nematode of cattle. The results showed that the free-living nematode Panagrellus sp. was the most preyed upon, compared to H. placei, for all the fungal treatments. Also, variable predatory capacity was observed for different fungal isolates belonging to the same genus when applied to different nematode species.