RESUMO
Resilience of mammals to anthropogenic climate and land-use changes is associated with the maintenance of adequate responses of several fitness-related traits such as those related to immune functions. Isolated and combined effects of decreased food availability and increased ambient temperature can lead to immunosuppression and greater susceptibility to disease. Our study tested the general hypothesis that decreased food availability, increased ambient temperature and the combined effect of both factors would affect selected physiological and behavioral components associated with the innate immune system of fruit-eating bats (Carollia perspicillata). Physiological (fever, leukocytosis and neutrophil/lymphocyte ratio) and behavioral (food intake) components of the acute phase response, as well as bacterial killing ability of the plasma were assessed after immune challenge with lipopolysaccharide (LPS: 10 mg/kg) in experimental groups kept at different short-term conditions of food availability (ad libitum diet or 50% food-deprived) and ambient temperature (27 and 33°C). Our results indicate that magnitude of increase in body temperature was not affected by food availability, ambient temperature or the interaction of both factors, but the time to reach the highest increase took longer in LPS-injected bats that were kept under food restriction. The magnitude of increased neutrophil/lymphocyte ratio was affected by the interaction between food availability and ambient temperature, but food intake, total white blood cell count and bacterial killing ability were not affected by any factor or interaction. Overall, our results suggest that bacterial killing ability and most components of acute phase response examined are not affected by short-term changes in food availability and ambient temperature within the range evaluated in this study, and that the increase of the neutrophil/lymphocyte ratio when bats are exposed to low food availability and high ambient temperature might represent an enhancement of cellular response to deal with infection.
Assuntos
Quirópteros , Imunidade Inata , Lipopolissacarídeos , Temperatura , Animais , Quirópteros/imunologia , Quirópteros/fisiologia , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Neutrófilos/imunologia , Masculino , Ingestão de Alimentos , Frutas/imunologia , Temperatura Corporal , Reação de Fase Aguda/imunologiaRESUMO
The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1ß, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1ß, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.
Assuntos
Artralgia/imunologia , Febre de Chikungunya/imunologia , Interleucina-8/sangue , Reação de Fase Aguda/sangue , Reação de Fase Aguda/imunologia , Adolescente , Adulto , Artralgia/sangue , Febre de Chikungunya/sangue , Febre de Chikungunya/complicações , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
The synthesis and characterization of latex-protein complexes (LPC), from the acute phase recombinant antigen P35 (P35Ag) of Toxoplasma gondii and "core-shell" carboxylated or polystyrene (PS) latexes (of different sizes and charge densities) are considered, with the aim of producing immunoagglutination reagents able to detect recently acquired toxoplasmosis. Physical adsorption (PA) and chemical coupling (CC) of P35Ag onto latex particles at different pH were investigated. Greater amounts of adsorbed protein were obtained on PS latexes than on carboxylated latexes, indicating that hydrophobic forces govern the interactions between the protein and the particle surface. In the CC experiments, the highest amount of bound protein was obtained at pH 6, near the isoelectric point of the protein (IP=6.27). At this pH, it decreased both the repulsion between particle surface and protein, and the repulsion between neighboring molecules. The LPC were characterized and the antigenicity of the P35Ag protein coupled on the particles surface was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA). Results from ELISA showed that the P35Ag coupled to the latex particles surface was not affected during the particles sensitization by PA and CC and the produced LPC were able to recognize specific anti-P35Ag antibodies present in the acute phase of the disease.
Assuntos
Reação de Fase Aguda/imunologia , Antígenos de Protozoários/imunologia , Látex/imunologia , Poliestirenos/imunologia , Proteínas Recombinantes/imunologia , Toxoplasma/imunologia , Toxoplasmose/diagnóstico , Adsorção , Eletroforese , Ensaio de Imunoadsorção Enzimática , Concentração de Íons de Hidrogênio , Látex/química , Poliestirenos/síntese química , Poliestirenos/química , Toxoplasmose/imunologia , Toxoplasmose/parasitologiaRESUMO
Chagas disease develops upon infection with the protozoan parasite Trypanosoma cruzi and undergoes an acute phase characterized by massive parasite replication and the presence of parasites in the blood. This condition is known as acute phase parasitemia. This initial stage may result in a cure, in the development of the chronic stages of the disease or in the death of the infected host. Despite intensive investigation related to the characterization of the acute and chronic phases of the disease, the cause-effect relationship of acute phase parasitemia to the outcome of the disease is still poorly understood. In this study, we artificially generated a heterogeneously controlled mouse population by intercrossing F1 mice obtained from a parental breeding of highly susceptible A/J with highly resistant C57BL/6 mouse strains. This F2 population was infected and used to assess the correlation of acute phase parasitemia with the longevity of the animals. We used nonparametric statistical analyses and found a significant association between parasitemia and mortality. If males and females were evaluated separately, we found that the former were more susceptible to death, although parasitemia was similar in males and females. In females, we found a strong negative correlation between parasitemia and longevity. In males, however, additional factors independent of parasitemia may favor mouse mortality during the development of the disease. The correlations of acute phase parasitemia with mortality reported in this study may facilitate an appropriate prognostic approach to the disease in humans. Moreover, these results illustrate the complexity of the mammalian genetic traits that regulate host resistance during Chagas disease.
Assuntos
Reação de Fase Aguda/imunologia , Reação de Fase Aguda/parasitologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Parasitemia/imunologia , Parasitemia/parasitologia , Animais , Cruzamentos Genéticos , Feminino , Longevidade , Masculino , Camundongos Endogâmicos C57BL , Caracteres Sexuais , Análise de Sobrevida , Trypanosoma cruzi/fisiologiaRESUMO
The important role of the CD8(+) T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8(+) T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8(+) T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4(+) T-cell set points were observed in PHI subjects with higher HIV-specific CD8(+) T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1ß (MIP-1ß). All together, this study underscores the importance of CD8(+) T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.
Assuntos
Reação de Fase Aguda/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia , Argentina , Sequência de Bases , Biomarcadores/metabolismo , Citocinas/imunologia , ELISPOT , Antígenos HLA , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Estatísticas não Paramétricas , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologiaRESUMO
UNLABELLED: Acetaminophen (APAP) is a safe analgesic and antipyretic drug. However, APAP overdose leads to massive hepatocyte death. Cell death during APAP toxicity occurs by oncotic necrosis, in which the release of intracellular contents can elicit a reactive inflammatory response. We have previously demonstrated that an intravascular gradient of chemokines and mitochondria-derived formyl peptides collaborate to guide neutrophils to sites of liver necrosis by CXC chemokine receptor 2 (CXCR2) and formyl peptide receptor 1 (FPR1), respectively. Here, we investigated the role of CXCR2 chemokines and mitochondrial products during APAP-induced liver injury and in liver neutrophil influx and hepatotoxicity. During APAP overdose, neutrophils accumulated into the liver, and blockage of neutrophil infiltration by anti-granulocyte receptor 1 depletion or combined CXCR2-FPR1 antagonism significantly prevented hepatotoxicity. In agreement with our in vivo data, isolated human neutrophils were cytotoxic to HepG2 cells when cocultured, and the mechanism of neutrophil killing was dependent on direct contact with HepG2 cells and the CXCR2-FPR1-signaling pathway. Also, in mice and humans, serum levels of both mitochondrial DNA (mitDNA) and CXCR2 chemokines were higher during acute liver injury, suggesting that necrosis products may reach remote organs through the circulation, leading to a systemic inflammatory response. Accordingly, APAP-treated mice exhibited marked systemic inflammation and lung injury, which was prevented by CXCR2-FPR1 blockage and Toll-like receptor 9 (TLR9) absence (TLR9(-/-) mice). CONCLUSION: Chemokines and mitochondrial products (e.g., formyl peptides and mitDNA) collaborate in neutrophil-mediated injury and systemic inflammation during acute liver failure. Hepatocyte death is amplified by liver neutrophil infiltration, and the release of necrotic products into the circulation may trigger a systemic inflammatory response and remote lung injury.
Assuntos
Reação de Fase Aguda/metabolismo , Quimiocinas/metabolismo , DNA Mitocondrial/sangue , Falência Hepática Aguda/imunologia , Fígado/patologia , Neutrófilos/imunologia , Receptores de Formil Peptídeo/metabolismo , Acetaminofen , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/imunologia , Reação de Fase Aguda/imunologia , Adolescente , Adulto , Análise de Variância , Animais , Movimento Celular , Quimiocinas/sangue , Quimiocinas/imunologia , Criança , Técnicas de Cocultura , Feminino , Células Hep G2 , Humanos , Interleucina-8/sangue , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas Mitocondriais/imunologia , Proteínas Mitocondriais/metabolismo , Necrose/imunologia , Receptores de Formil Peptídeo/imunologia , Receptores de Interleucina-8B/sangue , Receptores de Interleucina-8B/imunologia , Receptores de Interleucina-8B/metabolismo , Transdução de Sinais , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia , Adulto JovemRESUMO
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
A sex steroid-dependent modulation of the immune function in mammals is accepted, and evidence suggests that while estrogens enhance, androgens inhibit the immune response. The aim of this study was to explore in the adult male rat the effect of either neonatal flutamide (FTM) treatment or prepubertal orchidectomy (ODX) on endocrine markers in the basal condition and peripheral tumor necrosis factor alpha (TNFα) levels during inflammatory stress. For these purposes, (1) 5-day-old male rats were subcutaneously injected with either sterile vehicle alone or containing 1.75 mg FTM, and (2) 25-day-old male rats were sham operated or had ODX. Rats were sacrificed (at 100 days of age) in the basal condition for determination of peripheral metabolite levels. Additional rats were intravenously injected with bacterial lipopolysaccharide (LPS; 25 µg/kg body weight, i.v.) and bled for up to 4 h. Data indicate that (1) ODX increased peripheral glucocorticoid levels and reduced those of testosterone, whereas FTM-treated rats displayed low circulating leptin concentrations, and (2) LPS-induced TNFα secretion in plasma was significantly enhanced in the FTM and ODX groups. Our study supports that neonatal FTM treatment affected adiposity function, and adds data maintaining that androgens have a suppressive role in proinflammatory cytokine release in plasma during inflammation.
Assuntos
Reação de Fase Aguda/imunologia , Citocinas/metabolismo , Endotoxemia/imunologia , Endotoxemia/metabolismo , Neuroimunomodulação/fisiologia , Testosterona/imunologia , Reação de Fase Aguda/sangue , Animais , Animais Recém-Nascidos , Castração , Ensaio de Imunoadsorção Enzimática , Glucocorticoides/sangue , Leptina/sangue , Lipopolissacarídeos/toxicidade , Masculino , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Testosterona/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Wide-ranging activation of the innate immune system causing chronic low-grade inflammation is closely involved not only in the pathogenesis of type 2 diabetes mellitus and its complications, through an ongoing cytokine-induced acute-phase response, but also in the pathogenesis of periodontal diseases, whereby cytokines play a central role in the host's response to the periodontal biofilm. Although there is extensive knowledge about the pathways through which diabetes affects periodontal status, less is known about the impact of periodontal diseases on the diabetes-related inflammatory state. This review attempts to explain the immunobiological connection between periodontal diseases and type 2 diabetes mellitus, exploring the mechanisms through which periodontal infection can contribute to the low-grade general inflammation associated with diabetes (thus aggravating insulin resistance) and discussing the impact of periodontal treatment on glycemic control in people living with both diabetes and periodontal disease.
Assuntos
Diabetes Mellitus Tipo 2/imunologia , Periodontite/imunologia , Reação de Fase Aguda/imunologia , Biofilmes , Citocinas/imunologia , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Imunidade Inata/imunologia , Mediadores da Inflamação/imunologia , Resistência à Insulina/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Periodontite/microbiologia , Periodontite/terapiaRESUMO
Corticosteroids have been proposed for decades as adjunctive therapy of severe infections. These drugs have complex mechanisms of action involving anti-inflammatory and vasoactive properties. However, due to discordant results from clinical studies, the use of corticosteroids to treat patients with severe infections is still a matter of intense debate in the scientific and medical community. In the present article, we review the underlying mechanisms related to the potential benefits of corticosteroids and their impact on clinical management of severe sepsis.