RESUMEN
Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects.
Asunto(s)
Anticuerpos Antibacterianos , Inmunización Pasiva , Inmunoglobulinas , Leptospira , Leptospirosis , Animales , Cricetinae , Femenino , Anticuerpos Antibacterianos/inmunología , Pollos/inmunología , Modelos Animales de Enfermedad , Doxiciclina/uso terapéutico , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Yema de Huevo/inmunología , Inmunización Pasiva/métodos , Inmunoglobulinas/inmunología , Inmunoglobulinas/administración & dosificación , Riñón/patología , Riñón/inmunología , Riñón/microbiología , Leptospira/inmunología , Leptospirosis/inmunología , Leptospirosis/prevención & control , Leptospirosis/terapia , Hígado/inmunología , Hígado/patología , Hígado/microbiología , Mesocricetus , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificaciónRESUMEN
African swine fever (ASF), a highly contagious, deadly infectious disease, has caused huge economic losses to animal husbandry with a 100% mortality rate of the most acute and acute infection, which is listed as a legally reported animal disease by the World Organization for Animal Health (OIE). African swine fever virus (ASFV) is the causative agent of ASF, which is the only member of the Asfarviridae family. Ornithodoros soft ticks play an important role in ASFV transmission by active biological or mechanical transmission or by passive transport or ingestion, particularly in Africa, Europe, and the United States. First, this review summarized recent reports on (1) tick species capable of transmitting ASFV, (2) the importance of ticks in the transmission and epidemiological cycle of ASFV, and (3) the ASFV strains of tick transmission, to provide a detailed description of tick-borne ASFV. Second, the dynamics of tick infection with ASFV and the tick-induced immune suppression were further elaborated to explain how ticks spread ASFV. Third, the development of the anti-tick vaccine was summarized, and the prospect of the anti-tick vaccine was recapitulated. Then, the marked attenuated vaccine, ASFV-G-ΔI177L, was compared with those of the anti-tick vaccine to represent potential therapeutic or strategies to combat ASF.
Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Virus de la Fiebre Porcina Clásica , Ornithodoros , Porcinos , Animales , Fiebre Porcina Africana/epidemiología , Fiebre Porcina Africana/prevención & control , África/epidemiologíaRESUMEN
Leptospirosis is a global zoonotic disease with outcomes ranging from subclinical infection to fatal Weil's syndrome. In addition to antibiotics, some immune activators have shown protective effects against leptospirosis. However, the unclear relationship between Leptospira and cytokines has limited the development of antileptospiral immunomodulators. In this study, the particular role of interleukin-10 (IL-10) in leptospirosis was explored by using IL-10-defective (IL-10-/-) hamsters. After Leptospira infection, an improved survival rate, reduced leptospiral burden, and alleviation of organ lesions were found in IL-10-/- hamsters compared with wild-type (WT) hamsters. In addition, the levels of expression of the IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) genes and the level of nitric oxide (NO) were higher in IL-10-/- hamsters than in WT hamsters. Our results indicate that IL-10 deficiency protects hamsters from Leptospira infection.
Asunto(s)
Leptospira interrogans , Leptospira , Leptospirosis , Animales , Cricetinae , Citocinas/genética , Modelos Animales de Enfermedad , Factores Inmunológicos , Interleucina-10/genética , Leptospirosis/patologíaRESUMEN
Chronic leptospirosis usually occurs during sublethal doses infection of susceptible animal and reservoir host, which typical symptom is interstitial nephritis, and leptospira urine, contaminating the environment and threatening other susceptible animals and humans. Dipotassium glycyrrhizinate (DG) is a replacement for glycyrrhizic acid, which exhibits anti-inflammation, immunomodulation effects. This study is to investigate whether DG relieves leptospira-induced nephritis. In vitro, DG inhibited the leptospira-induced transcription levels of IL-1ß, IL-6, TNF-α, RANTES, MCP-1 and iNOS, and protein levels of IL-1ß and TNF-α, and downregulated NF-κB and MAPK pathway in TCMK-1 cells. In vivo, DG attenuated the kidney histopathological change and downregulated the expression of IL-1ß and TNF-α, as well as reduced kidney leptospiral burden. In summary, DG alleviated leptospira-induced inflammation through inhibitory NF-κB and MAPK pathway, and DG decreased the renal colonization of leptospires in mice.
Asunto(s)
Leptospira interrogans , Leptospira , Leptospirosis , Nefritis , Animales , Ácido Glicirrínico/farmacología , Leptospirosis/tratamiento farmacológico , RatonesRESUMEN
Leptospirosis is a worldwide zoonotic disease that causes acute kidney injury, liver disease, bleeding disorders, and even death. Treatment of the disease is largely dependent on the use of antibiotics, but recent studies on pathogenesis of leptospirosis have shown that immunomodulation may also be an effective treatment for this disease. Since the delay in inflammation correlates with higher pathogenicity of leptospira, we studied the effect of inducing inflammation on leptospirosis by using TLR4 activator LPS. In accordance with our hypothesis, treatment with LPS protected against leptospirosis by enhancing the inflammatory response in hamsters. The gene expression levels of TLR2, TLR4, NLRP3 and inflammatory factors were higher in LPS-treated group during leptospira infection in hamsters. Although the levels of NO and iNOS were higher in LPS-treated group than in Leptospira-infected group, the protective effect induced by LPS is iNOS-independent. Treatment with LPS induced higher anti-leptospira IgG level than infection with leptospira alone. Then, expressions of costimulatory molecules and maturation markers were analysed. The data showed that treatment with LPS enhanced the expression of CD40, CD80 and CD86. Our results indicate that increased inflammation induced by LPS derived from Escherichia coli (E. coli) protects against leptospirosis in hamsters.
Asunto(s)
Escherichia coli/inmunología , Leptospirosis/prevención & control , Lipopolisacáridos/inmunología , Enfermedad Aguda , Animales , Cricetinae , Femenino , Humanos , Leptospira/inmunología , Leptospira/fisiología , Leptospirosis/inmunología , Leptospirosis/microbiología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunologíaRESUMEN
Leptospirosis, caused by pathogenic Leptospira species, has emerged as an important neglected zoonotic disease. Few studies have reported the preventable effects of immunoregulators, except for antibiotics, against leptospirosis. Generally, immunostimulatory agents are considered effective for enhancing innate immune responses. Many studies have found that beta-glucan (ß-glucan) could be a potent and valuable immunostimulant for improving immune responses and controlling diseases. In this study, we investigated the preventable role of ß-glucan against Leptospira infection in hamsters. First, ß-glucan was administered 24 h prior to, during and after infection. The results showed that ß-glucan increased the survival rate to 100%, alleviated tissue injury, and decreased leptospire loads in target organs. Additionally, we found using quantitative real-time PCR that application of ß-glucan significantly enhanced the expression of Toll-like receptor (TLR) 2, interleukin (IL)-1ß and iNOS at 2 dpi (days post infection) and reduced the increase of TLR2, IL-1ß and iNOS induced by Leptospira at 5 dpi. Furthermore, to induce memory immunity, ß-glucan was administered 5 days prior to infection. ß-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that ß-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1ß and IL-6) in vitro, indicating that ß-glucan induces an enhanced inflammatory response against Leptospira infection. These results indicate that administration of ß-glucan and other immunostimulants could be potential valuable options for the control of Leptospira infection.