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1.
Methods Mol Biol ; 2414: 363-372, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34784046

RESUMO

There is no vaccine available to prevent Neisseria gonorrhoeae infection, however there is currently a high level of interest in developing gonococcal vaccines due to the increasing number of cases and continuing emergence of antimicrobial resistance worldwide. A key aspect of vaccine development is the investigation of the functional immune response raised to the vaccine targets under investigation. Here, we describe two assays used to assess the functional immune response raised against gonococcal vaccine targets: the serum bactericidal assay (SBA) and the opsonophagocytic assay (OPA).


Assuntos
Gonorreia , Anticorpos Antibacterianos , Vacinas Bacterianas , Atividade Bactericida do Sangue , Gonorreia/prevenção & controle , Humanos , Neisseria gonorrhoeae/imunologia
2.
PLoS Negl Trop Dis ; 15(7): e0009605, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34324509

RESUMO

BACKGROUND: Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb. METHODS: We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv). RESULTS: The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. CONCLUSIONS: Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.


Assuntos
Atividade Bactericida do Sangue , Antígenos CD4/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Antígenos CD4/genética , Estudos de Casos e Controles , Fatores de Transcrição Forkhead/genética , Humanos , Subunidade alfa de Receptor de Interleucina-2/genética , Linfócitos T Reguladores
3.
J Exp Zool A Ecol Integr Physiol ; 335(6): 541-551, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34018702

RESUMO

The inflammatory response is a complex process that relies on interactions among multiple endocrine and immune modulators. Studies incorporating time-related and integrative endocrine and immune responses to an immune challenge might shed light on the characterization of the phases of the inflammatory response in anurans. The present study investigated time-related changes (1, 3, 6, and 18 h post-challenge) in plasma corticosterone (CORT), melatonin (MEL) and testosterone (T) levels, phagocytosis percentage (PP), plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR) following a lipopolysaccharide (LPS) immune challenge in Rhinella diptycha toads. Our results showed the response to LPS injection was characterized by increased CORT, PP, BKA, and NLR, with a concomitant decrease in plasma MEL and T. Increased CORT was more pronounced at 6 and 18 h, while increased NLR was observed only 18 h post-LPS injection. Meanwhile, plasma MEL and T decreased independently of the time post-LPS injection. Additionally, toads in better body condition showed higher BKA and PP in the LPS-treated group, regardless of the time postinjection. Our results show that toads (R. diptycha) were sensitive to the LPS challenge, mounting an inflammatory response, which started quickly (after 1 h) and developed over time and was influenced by body condition. These results demonstrate a time-related hormonal and immune variation as a consistent pattern of activation of the immune system, as well as of hypothalamic-pituitary-adrenal/interrenal and immune-pineal axes following an immune challenge more deeply studied in mammals, suggesting the evolutionary conservation of the regulatory mechanisms for tetrapod vertebrates.


Assuntos
Bufonidae/imunologia , Corticosterona/sangue , Imunomodulação/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Melatonina/sangue , Animais , Atividade Bactericida do Sangue , Inflamação/induzido quimicamente , Inflamação/imunologia , Linfócitos/fisiologia , Masculino , Neutrófilos/fisiologia , Fagocitose , Testosterona/sangue
4.
Ann Clin Microbiol Antimicrob ; 20(1): 40, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044843

RESUMO

BACKGROUND AND AIM: Treatment of burn wound infections has become a global challenge due to the spread of multidrug-resistant bacteria; therefore, the development of new treatment options for the mentioned infections is essential. Platelets have drawn much attention for this purpose because they are a safe and cost-effective source of different antimicrobial peptides and growth factors. The present study evaluated antibacterial effects and wound healing properties of Platelet-derived Biomaterial (PdB) against Acinetobacter baumannii and Klebsiella pneumoniae burn wound infections. METHODS: PdB was prepared through the freezing and thawing process and then, in vitro antibacterial effect was determined by disk diffusion and broth microdilution methods. Afterward, burn wound was inflicted on 56 rats, infected with both bacteria, and topical administration was performed to evaluate antibacterial effects and wound healing properties of PdB. RESULTS: In vitro results showed that PdB inhibited the growth of A. baumannii in the highest dose (0.5), while we did not detect any inhibitory effects against K. pneumoniae. By contrast, PdB significantly inhibited the growth of bacteria in treated animal wounds compared to the control groups (P value < 0.05). Macroscopic assessments pointed to the significant enhancement of wound closure in the treated animals. In addition, histopathological examination demonstrated that treatment of rats with PdB led to a considerable increase in re-epithelialization and attenuated the formation of granulation tissue (P value < 0.05). CONCLUSION: The use of topical PdB is an attractive strategy for treating A. baumannii and K. pneumoniae burn wound infections because it inhibits bacterial growth and promotes wound healing properties.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Extratos Celulares/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Animais , Materiais Biocompatíveis/uso terapêutico , Atividade Bactericida do Sangue , Plaquetas/química , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Masculino , Ratos , Ratos Wistar
5.
Mar Drugs ; 19(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572960

RESUMO

Bio-nanotechnology employing bio-sourced nanomaterial is an emerging avenue serving the field of fish medicine. Marine-sourced chitosan nanoparticles (CSNPs) is a well-known antimicrobial and immunomodulatory reagent with low or no harm side effects on fish or their human consumers. In this study, in vitro skin mucus and serum antibacterial activity assays along with intestinal histology, histochemical, and gene expression analyses were performed to evaluate the impact of dietary CSNPs (5 g kg-1 dry feed) on rainbow trout resistance against 'enteric redmouth' disease. Two treatment conditions were included; short-term prophylactic-regimen for 21 days before the bacterial challenge, and long-term therapeutic-regimen for 21 days before the challenge and extended for 28 days after the challenge. Our results revealed higher antibacterial defense ability and positive intestinal histochemical and molecular traits of rainbow trout after dietary CSNPs. The prophylactic-regimen improved trout health while the therapeutic regimen improved their disease resistance and lowered their morbidity. Therefore, it is anticipated that CSNPs is an effective antibacterial and immunomodulatory fish feed supplement against the infectious threats. However, the CSNPs seem to be more effective in the therapeutic application rather than being used for short-term prophylactic applications.


Assuntos
Antibacterianos/administração & dosagem , Quitosana/administração & dosagem , Doenças dos Peixes/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Intestinos/imunologia , Nanopartículas/administração & dosagem , Oncorhynchus mykiss/imunologia , Animais , Atividade Bactericida do Sangue , Quitosana/farmacologia , Suplementos Nutricionais , Doenças dos Peixes/imunologia , Intestinos/patologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-33321177

RESUMO

Species introduced by human activities can alter the normal functioning of ecosystems promoting negative impacts on native biodiversity, as they can rapidly expand their population size, demonstrating phenotypic plasticity and possible adaptive capacity to novel environments. Twenty years ago, the guttural toad, Sclerophrys gutturalis, was introduced to a peri-urban area of Cape Town, with cooler and drier climatic characteristics than its native source population, Durban, South Africa. Our goal was to understand the phenotypic changes, in terms of physiology and immunity, of populations in native and novel environments. We evaluated body index (BI), field hydration level, plasma corticosterone levels (CORT), proportion of neutrophils: lymphocytes (N: L), plasma bacterial killing ability (BKA), and hematocrit (HTC) in the field, and after standardized stressors (dehydration and movement restriction) in males from the native and invasive populations. Toads from the invasive population presented lower BI and tended to show a lower field hydration state, which is consistent with living in the drier environmental conditions of Cape Town. Additionally, invasive toads also showed higher BKA and N:L ratio under field conditions. After exposure to stressors, invasive animals presented higher BKA than the natives. Individuals from both populations showed increased CORT after dehydration, an intense stressor for these animals. The highest BKA and N:L ratio in the field and after submission to stressors in the laboratory shows that the invasive population has a phenotype that might increase their fitness, leading to adaptive responses in the novel environment and, thus, favoring successful dispersion and population increase.


Assuntos
Bufonidae/fisiologia , Desidratação/fisiopatologia , Espécies Introduzidas , Estresse Fisiológico , Equilíbrio Hidroeletrolítico , Animais , Atividade Bactericida do Sangue , Bufonidae/imunologia , Contagem de Linfócitos , Neutrófilos/citologia , África do Sul
7.
Artigo em Inglês | MEDLINE | ID: mdl-33326846

RESUMO

Host's defense against external challenges activates an inflammatory response regulated by a set of chemical signals, including hormones. These immunomodulatory hormones, such as corticosterone, testosterone, and melatonin, trigger the systemic immune responses responsible for inflammatory assembly and resolution. This study aimed to investigate the effects of an immune challenge on endocrine and innate immune responses in the bullfrog (Lithobates catesbeianus). Adult males were intraperitoneally injected with lipopolysaccharide (LPS; 2 mg/kg) or saline, and blood samples were collected 6 and 24 h after injection for measurement of neutrophil/lymphocyte ratio, blood leukocyte phagocytosis, plasma bacterial killing ability, and plasma levels of corticosterone, melatonin, and testosterone. Our results showed LPS-induced increased neutrophil/lymphocyte ratio and leukocyte phagocytosis, and decreased melatonin and testosterone plasma levels, which were more pronounced 24 h after injection. Overall, we conclude that LPS intraperitoneal injection can activate the innate immune response and modulate the hormonal profile of the bullfrogs, with effects more pronounced 24 h than 6 h after treatment.


Assuntos
Lipopolissacarídeos/farmacologia , Linfócitos/imunologia , Melatonina/sangue , Neutrófilos/imunologia , Ranidae/fisiologia , Testosterona/sangue , Animais , Atividade Bactericida do Sangue , Injeções Intraperitoneais , Lipopolissacarídeos/administração & dosagem , Masculino , Ranidae/imunologia
8.
J Exp Zool A Ecol Integr Physiol ; 333(10): 767-778, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33369285

RESUMO

Climate change and emerging infectious diseases are often described as the main factors associated with the worldwide amphibian population decline. In this context, rising temperatures due to global warming might act as a chronic stressor for many amphibians, leading to immunosuppression. This study aimed to characterize the thermal sensitivity of the Bullfrog's (Lithobates catesbeianus) immune response and the effect of acclimation at different temperatures on it. Plasma bacterial killing ability (BKA) and phagocytosis activity of blood leukocytes were measured at different incubation temperatures (5-40°C) in individuals kept at 28°C and 34°C. First, all individuals were held under 28°C and sampled on the 16th day. Subsequently, one group was kept at 28°, and the other one was transferred to 34°C. Both groups were sampled at 83 and 106 days of maintenance. Plasma corticosterone (CORT) and testosterone (T) were assessed to evidence thermal stress and possible endocrine correlates of immune changes over time. The incubation temperature affected BKA both on animals kept at 28°C and 34°C, with maximum values at lower temperatures (5-20°C). Phagocytosis activity was constant over the range of assay temperatures. Immune and endocrine variables decreased over time in both thermal regimes, but frogs maintained at 34°C showed lower T and immunosuppression, evidencing stress response. Therefore, exposure to high temperatures might decrease immune function in bullfrogs due to chronic stress response and by exposition to temperatures of lower performance according to the thermal sensitivity curve, which might increase vulnerability to diseases in this anuran species.


Assuntos
Rana catesbeiana/imunologia , Animais , Atividade Bactericida do Sangue , Corticosterona/sangue , Citometria de Fluxo , Masculino , Fagocitose , Rana catesbeiana/fisiologia , Temperatura , Testosterona/sangue
9.
J Exp Zool A Ecol Integr Physiol ; 333(10): 820-828, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33075211

RESUMO

Longevity patterns in most vertebrates suggest that females benefit most from maintenance investment. A reversed longevity pattern in loggerhead musk turtles (Sternotherus minor) allowed us to test trade-offs between maintenance and survivorship. We tested the hypothesis that the sex with greater longevity has greater maintenance than the sex with shorter longevity. We also compared the following parameters between sexes: Bactericidal ability (BA) and heterophil:lymphocyte ratios (HLR). Baseline blood samples were collected from turtles in the field; a subset of turtles was returned to a laboratory for experiments of acquired immune responses to sheep red blood cells (SRBC). We found no support for the original hypothesis of reversal in sex-dependent immune trade-offs (difference between sex SRBC titers: p = .102; interaction between treatment and sex: p = .177; difference between treatments: p < .001; effect of sex on BA: p = .830; effect of sex on HLR: p = .717). However, we did find support for sex-dependent differences in immunity in the relationship between HLR and body condition (BCI) (effect of BCI on HLR: p = .015). In field conditions, we found that males with higher body condition indices express stressed phenotypes more than males with lower body condition indices (p = .002). However, females expressed similar stress loads across all body conditions (p = .900). Testosterone concentrations were assayed in free-living turtles and were not related to any of the immune parameters. Our results suggest that the immune systems play an important role in balancing sex-specific responses to different selective pressures in S. minor.


Assuntos
Imunidade Adaptativa/imunologia , Imunidade Inata/imunologia , Tartarugas/imunologia , Animais , Atividade Bactericida do Sangue , Feminino , Testes de Hemaglutinação , Contagem de Leucócitos , Longevidade/imunologia , Masculino , Fatores Sexuais , Testosterona/sangue
10.
Benef Microbes ; 11(6): 561-572, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33032469

RESUMO

The use of antibiotics to prevent bovine mastitis is responsible for the emergence and selection of resistant strains. Lactic acid bacteria (LAB) could be introduced into animal feed as an alternative prevention method that would bypass the risk of resistance development. In previous research, we demonstrated that two probiotic LAB strains isolated from bovine milk were capable of stimulating the production of antibodies and the host's immune cellular response in the udder. The present study aimed to elucidate whether the antibodies of animals inoculated with these strains were able to increase phagocytosis by neutrophils and inhibit the growth of different mastitis-causing pathogens. Moreover, the effect of LAB on the expression of pro-inflammatory cytokines was assessed. Ten animals were inoculated intramammarily with 106 cells of the two strains at dry-off. The blood serum was tested for its ability to opsonize bovine mastitis pathogens, the in vitro bactericidal activity of bovine blood and milk against these pathogens was determined, and cytokine mRNA expression was quantified in milk somatic cells. The inoculated animals did not show abnormal signs of sensitivity to the LAB. Their blood serum significantly enhanced the phagocytosis of Staphylococcus spp. and the LAB. Escherichia coli and Streptococcus uberis were inhibited by the milk serum but not the blood serum, whereas Staphylococcus aureus and Staphylococcus haemolyticus were inhibited by both. In regard to cytokine expression, interleukin (IL)-1ß increased markedly for up to 4 h post-inoculation, and an increase in IL-8 was observed 4, 12 and 24 h after inoculation. Tumour necrosis factor-α mRNA increased 1 and 2 h after inoculation and a significant difference was registered at 6 h for interferon-γ. This rapid immunomodulatory response shows that inoculating animals with LAB at dry-off, when they are especially susceptible, could be a useful strategy for the prevention of bovine mastitis.


Assuntos
Anticorpos Antibacterianos/imunologia , Bovinos/imunologia , Lactobacillales , Glândulas Mamárias Animais/imunologia , Mastite Bovina/prevenção & controle , Probióticos , Animais , Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Bovinos/microbiologia , Citocinas/genética , Citocinas/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/imunologia , Feminino , Lactobacillales/imunologia , Glândulas Mamárias Animais/microbiologia , Mastite Bovina/imunologia , Mastite Bovina/microbiologia , Leite/imunologia , Leite/metabolismo , Neutrófilos/imunologia , Fagocitose , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/imunologia , Streptococcus/crescimento & desenvolvimento , Streptococcus/imunologia
11.
Microbiology (Reading) ; 166(11): 1088-1094, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33095698

RESUMO

Staphylococcus aureus is a frequent cause of invasive human infections such as bacteraemia and infective endocarditis. These infections frequently relapse or become chronic, suggesting that the pathogen has mechanisms to tolerate the twin threats of therapeutic antibiotics and host immunity. The general stress response of S. aureus is regulated by the alternative sigma factor B (σB) and provides protection from multiple stresses including oxidative, acidic and heat. σB also contributes to virulence, intracellular persistence and chronic infection. However, the protective effect of σB on bacterial survival during exposure to antibiotics or host immune defences is poorly characterized. We found that σB promotes the survival of S. aureus exposed to the antibiotics gentamicin, ciprofloxacin, vancomycin and daptomycin, but not oxacillin or clindamycin. We also found that σB promoted staphylococcal survival in whole human blood, most likely via its contribution to oxidative stress resistance. Therefore, we conclude that the general stress response of S. aureus may contribute to the development of chronic infection by conferring tolerance to both antibiotics and host immune defences.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus/fisiologia , Estresse Fisiológico/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Atividade Bactericida do Sangue , Teste de Complementação Genética , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Mutação , Explosão Respiratória , Fator sigma/genética , Fator sigma/metabolismo , Staphylococcus aureus/efeitos dos fármacos
12.
Front Immunol ; 11: 2122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983170

RESUMO

Moraxella catarrhalis is a human-specific commensal of the respiratory tract and an opportunistic pathogen. It is one of the leading cause of otitis media in children and of acute exacerbations in patients with chronic obstructive pulmonary disease, resulting in significant morbidity and economic burden. Vaccines and new immunotherapeutic strategies to treat this emerging pathogen are needed. Complement is a key component of innate immunity that mediates the detection, response, and subsequent elimination of invading pathogens. Many pathogens including M. catarrhalis have evolved complement evasion mechanisms, which include the binding of human complement inhibitors such as C4b-binding protein (C4BP) and Factor H (FH). Inhibiting C4BP and FH acquisition by M. catarrhalis may provide a novel therapeutic avenue to treat infections. To achieve this, we created two chimeric proteins that combined the Moraxella-binding domains of C4BP and FH fused to human immunoglobulin Fcs: C4BP domains 1 and 2 and FH domains 6 and 7 fused to IgM and IgG Fc, respectively. As expected, FH6-7/IgG displaced FH from the bacterial surface while simultaneously activating complement via Fc-C1q interactions, together increasing pathogen elimination. C4BP1-2/IgM also increased serum killing of the bacteria through enhanced complement deposition, but did not displace C4BP from the surface of M. catarrhalis. These Fc fusion proteins could act as anti-infective immunotherapies. Many microbes bind the complement inhibitors C4BP and FH through the same domains as M. catarrhalis, therefore these Fc fusion proteins may be promising candidates as adjunctive therapy against many different drug-resistant pathogens.


Assuntos
Proteína de Ligação ao Complemento C4b/farmacologia , Fator H do Complemento/farmacologia , Fragmentos Fc das Imunoglobulinas/farmacologia , Moraxella catarrhalis/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Animais , Ligação Competitiva , Atividade Bactericida do Sangue , Células CHO , Complemento C3b/análise , Complemento C3d/análise , Proteína de Ligação ao Complemento C4b/genética , Proteína de Ligação ao Complemento C4b/metabolismo , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Cricetinae , Cricetulus , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Imunoglobulina G/farmacologia , Imunoglobulina M/genética , Imunoglobulina M/metabolismo , Imunoglobulina M/farmacologia , Moraxella catarrhalis/metabolismo , Ligação Proteica , Domínios Proteicos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
13.
J Exp Zool A Ecol Integr Physiol ; 333(10): 732-743, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32959993

RESUMO

Reptiles rely on thermal heat exchange to achieve body temperatures (Tbody ) conducive to maintaining homeostasis. Diurnal changes in the thermal environment are therefore liable to influence allostatic mediation of survival processes (e.g., immunity) during environmental challenges or stressors. However, the extent to which Tbody prompts individual variation in physiology remains largely unexplored in reptiles. Our study tested how circulating energy-mobilizing hormone, energy metabolites, and immunity can vary across basal and stress-induced allostatic states for plateau side-blotched lizards (Uta stansburiana uniformis) residing in a heterogeneous thermal environment. We collected baseline and acute stress blood samples from male lizards to compare changes in plasma corticosterone (CORT), glucose, and bacterial killing ability (BKA) in relation to each other and Tbody . We hypothesized each physiological parameter differs between allostatic states, whereby stress-induced activity increases from baseline. At basal and stress-induced states, we also hypothesized circulating CORT, glucose, and BKA directly correspond with each other and Tbody . We found both CORT and BKA increased while glucose instead decreased from acute stress. At basal and stress-induced allostatic states, we found CORT to be directly related to Tbody while BKA was inversely related to CORT. We also found BKA and glucose were directly related at baseline, but inversely related following acute stress. Overall, these results demonstrate allostatic outcomes from acute stress in a free-living reptile and the role of temperature in mediating energetic state and immunity. Future research on reptilian allostasis should consider multiple environmental conditions and their implications for physiological performance and survival.


Assuntos
Metabolismo Energético/fisiologia , Glucocorticoides/metabolismo , Lagartos/imunologia , Animais , Atividade Bactericida do Sangue , Glicemia/análise , Temperatura Corporal/fisiologia , Corticosterona/sangue , Meio Ambiente , Lagartos/metabolismo , Lagartos/fisiologia , Masculino , Estresse Fisiológico/imunologia , Estresse Fisiológico/fisiologia , Temperatura
14.
Pharmacol Res ; 160: 105149, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822868

RESUMO

Cancer chemotherapy induced neutropenia (CCIN) is one of the most common toxicity caused by cytotoxic anticancer agents. Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical practice, the infection and infection-related mortality rate is still high for lack of functionally mature neutrophils. Saikosaponin d (SSD) is one of the major bioactive constituents of Radix Bupleuri (RB), which exerts immune-modulatory properties. We explored the function of SSD in CCIN therapy, we found that SSD contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo. Network pharmacology was employed to explore the mechanism, 61 signal pathways might play an important role in CCIN treatment. Western Blot was employed to further confirm the potential pathway involved. We found CBL-ERK1/2 pathway was activated by SSD, followed by upregulating PU.1 and CEBPß expression and leading to neutrophil differentiation. Our findings suggest a natural regimen SSD which could regenerate microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2, providing a rationale for future therapeutic approaches.


Assuntos
Antineoplásicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Proteína Oncogênica v-cbl/efeitos dos fármacos , Saponinas/uso terapêutico , Animais , Atividade Bactericida do Sangue , Proteína beta Intensificadora de Ligação a CCAAT/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Controle de Infecções , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácido Oleanólico/uso terapêutico
15.
Nutrients ; 12(8)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32751919

RESUMO

Malnutrition is commonly associated with immunological deregulation, increasing the risk of infectious illness and death. The objective of this work was to determine the in vitro effects of heat-killed Lactobacillus casei IMAU60214 on monocyte-derived macrophages (MDMs) from well-nourished healthy children, well-nourished infected children and malnourished infected children, which was evaluated by an oxygen-dependent microbicidal mechanism assay of luminol-increase chemiluminescence and the secretion of tumor necrosis factor (TNF-α), interleukin (IL-1ß), IL-6 and IL-10, as well as phagocytosis using zymosan and as its antibacterial activity against Salmonella typhimurium, Escherichia coli and Staphylococcus aureus. We found that reactive oxygen species (ROS), secretion cytokines (TNFα, IL-1ß, IL-6 and IL-10 levels), phagocytosis and bactericidal capacity increased in all groups after pre-treatment with heat-killed L. casei IMAU60214 at a ratio of 500:1 (bacteria:MDM) over 24 h compared with MDM cells without pre-treatment. The results could indicate that heat-killed L. casei IMAU60214 is a potential candidate for regulating the immune function of macrophages.


Assuntos
Citocinas/imunologia , Transtornos da Nutrição do Lactente/imunologia , Lactobacillus casei/imunologia , Macrófagos/imunologia , Probióticos/farmacologia , Técnicas Bacteriológicas , Atividade Bactericida do Sangue/imunologia , Citocinas/sangue , Feminino , Temperatura Alta , Humanos , Lactente , Transtornos da Nutrição do Lactente/sangue , Transtornos da Nutrição do Lactente/microbiologia , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-1beta/sangue , Interleucina-1beta/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Macrófagos/microbiologia , Masculino , Fagocitose/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia
16.
J Exp Zool A Ecol Integr Physiol ; 333(10): 756-766, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32798287

RESUMO

As a free-living larval stage of a vertebrate, tadpoles are good subjects for the study of the development of physiological systems and the study of evolutionarily conserved, context-dependent responses to variable environments. While the basic components of innate and adaptive immune defenses in tadpoles are known, the impact of glucocorticoids on immune defenses in tadpoles is not well-studied. We completed four experiments to assess effects of elevation of corticosterone on humoral innate defenses and antibody-mediated immunity in southern leopard frog tadpoles (Lithobates sphenocephalus). To test humoral innate defense within the tadpoles exposed to short-term and long-term elevation of glucocorticoids, we exposed tadpoles to exogenous corticosterone for different lengths of time in each experiment (0-84 days). We used bacterial killing assays to assess humoral innate immune defense. To test antibody-mediated immune responses, we again exposed tadpoles to exogenous corticosterone, while also exposing them to Aeromonas hydrophila. We used A. hydrophila ELISA comparing IgM and IgY responses among groups. Plasma from corticosterone-dosed tadpoles killed more A. hydrophila than control tadpoles each following a short-term (14 day) and long-term (56 day) exposure to exogenous corticosterone. Conversely, corticosterone-dosed tadpoles had significantly lower IgM and IgY against A. hydrophila after 12 weeks. Our fourth experiment revealed that the lower IgY response is a product of weaker, delayed isotype switching compared with controls. These results show that elevated corticosterone has differential effects on innate and acquired immunity in larval southern leopard frogs, consistent with patterns in more derived vertebrates and in adult frogs.


Assuntos
Corticosterona/farmacologia , Imunidade Humoral/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Rana pipiens/imunologia , Aeromonas hydrophila/imunologia , Animais , Atividade Bactericida do Sangue/efeitos dos fármacos , Relação Dose-Resposta a Droga , Larva , Rana pipiens/sangue , Rana pipiens/fisiologia
17.
J Exp Zool A Ecol Integr Physiol ; 333(10): 779-791, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32488987

RESUMO

Cane toads (Rhinella marina) were introduced worldwide and have become invasive in multiple locations, representing a major driver of biodiversity loss through competition (food, shelter, territory), predation, and the poisoning of native species. These toads have been used in Australia as a model for studies concerning invasion biology and ecoimmunology, as longer-established (core) and invasion front (edge) populations show altered stress and immune response profiles. Although cane toads were also introduced into the United States in the 1950s, these patterns have yet to be evaluated for the populations spanning Florida. Toads introduced into Florida have dispersed primarily northward along a latitudinal gradient, where they encounter cooler temperatures that may further impact stress and immune differences between core and edge populations. In this study, we sampled cane toads from nine different locations spanning their invasion in Florida. Cane toads from southern populations showed higher plasma bacterial killing ability and natural antibody titers than the toads from the northern populations, indicating they have a better immune surveillance system. Also, southern toads were more responsive to a novel stressor (1 hr restraint), showing a higher increase in corticosterone levels. These results indicate that possible trade-offs have occurred between immune and stress responses as these toads have become established in northern cooler areas in Florida.


Assuntos
Bufo marinus/imunologia , Estresse Fisiológico/imunologia , Animais , Atividade Bactericida do Sangue , Bufo marinus/sangue , Bufo marinus/fisiologia , Corticosterona/sangue , Feminino , Florida , Testes de Hemaglutinação , Espécies Introduzidas , Linfócitos/fisiologia , Masculino , Neutrófilos/fisiologia , Estresse Fisiológico/fisiologia , Temperatura
18.
Infect Immun ; 88(8)2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32513855

RESUMO

The serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of Klebsiella pneumoniae to cause infection, but it is an incompletely understood virulence trait. Identifying and characterizing the factors responsible for preventing activation of, and killing by, serum complement could inform new approaches to treatment of K. pneumoniae infections. Here, we used functional genomic profiling to define the genetic basis of complement resistance in four diverse serum-resistant K. pneumoniae strains (NTUH-K2044, B5055, ATCC 43816, and RH201207), and explored their recognition by key complement components. More than 90 genes contributed to resistance in one or more strains, but only three, rfaH, lpp, and arnD, were common to all four strains. Deletion of the antiterminator rfaH, which controls the expression of capsule and O side chains, resulted in dramatic complement resistance reductions in all strains. The murein lipoprotein gene lpp promoted capsule retention through a mechanism dependent on its C-terminal lysine residue; its deletion led to modest reductions in complement resistance. Binding experiments with the complement components C3b and C5b-9 showed that the underlying mechanism of evasion varied in the four strains: B5055 and NTUH-K2044 appeared to bypass recognition by complement entirely, while ATCC 43816 and RH201207 were able to resist killing despite being associated with substantial levels of C5b-9. All rfaH and lpp mutants bound C3b and C5b-9 in large quantities. Our findings show that, even among this small selection of isolates, K. pneumoniae adopts differing mechanisms and utilizes distinct gene sets to avoid complement attack.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Carboxiliases/imunologia , Regulação Bacteriana da Expressão Gênica/imunologia , Genes Bacterianos , Evasão da Resposta Imune , Klebsiella pneumoniae/imunologia , Fatores de Alongamento de Peptídeos/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Atividade Bactericida do Sangue/imunologia , Carboxiliases/deficiência , Carboxiliases/genética , Complemento C3b/genética , Complemento C3b/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/genética , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Elementos de DNA Transponíveis , Perfilação da Expressão Gênica , Biblioteca Gênica , Humanos , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidade , Mutação , Fatores de Alongamento de Peptídeos/deficiência , Fatores de Alongamento de Peptídeos/genética , Análise de Sequência de DNA
19.
PLoS Pathog ; 16(6): e1008606, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32569291

RESUMO

An important effector function of the human complement system is to directly kill Gram-negative bacteria via Membrane Attack Complex (MAC) pores. MAC pores are assembled when surface-bound convertase enzymes convert C5 into C5b, which together with C6, C7, C8 and multiple copies of C9 forms a transmembrane pore that damages the bacterial cell envelope. Recently, we found that bacterial killing by MAC pores requires local conversion of C5 by surface-bound convertases. In this study we aimed to understand why local assembly of MAC pores is essential for bacterial killing. Here, we show that rapid interaction of C7 with C5b6 is required to form bactericidal MAC pores on Escherichia coli. Binding experiments with fluorescently labelled C6 show that C7 prevents release of C5b6 from the bacterial surface. Moreover, trypsin shaving experiments and atomic force microscopy revealed that this rapid interaction between C7 and C5b6 is crucial to efficiently anchor C5b-7 to the bacterial cell envelope and form complete MAC pores. Using complement-resistant clinical E. coli strains, we show that bacterial pathogens can prevent complement-dependent killing by interfering with the anchoring of C5b-7. While C5 convertase assembly was unaffected, these resistant strains blocked efficient anchoring of C5b-7 and thus prevented stable insertion of MAC pores into the bacterial cell envelope. Altogether, these findings provide basic molecular insights into how bactericidal MAC pores are assembled and how bacteria evade MAC-dependent killing.


Assuntos
Atividade Bactericida do Sangue , Membrana Celular/metabolismo , Parede Celular/metabolismo , Complemento C5/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Escherichia coli/metabolismo , Proteínas do Sistema Complemento/metabolismo , Células HEK293 , Humanos
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