RESUMO
Vibrio parahaemolyticus causes vibriosis in wide range of marine organisms, and is responsible for food borne illnesses in humans through consumption of contaminated uncooked/partially cooked seafood. Continued and widespread antibiotics usage to increase the productivity has led to antibiotics resistance development. This has necessitated the need to develop alternative methods to control its infection. Use of safe and effective vaccines against the virulence factors not only protects from infection, it also minimizes antibiotic usage. The colonization of V. parahaemolyticus in the host and disease development requires several adhesins present on the cell surface, and thereby make them attractive vaccine candidates. V. parahaemolyticus produces extracellular type 1 fimbriae that have been shown to play a role in adhesion, biofilm formation and virulence. FimH is one of the minor components of the type 1 fimbriae occurring on its very tip. Being present on the cell surface, it is highly immunogenic, and can be targeted as a potential vaccine candidate. The present study describes the immunogenic and vaccine potential of recombinant V. parahaemolyticus FimH (rVpFimH) expressed in E. coli. Immunization of BALB/c mice with the rVpFimH elicited a strong mixed immune response, T-cell memory (evidenced by antibody isotyping, cytokine profiling and T-cell proliferation assay), and agglutination positive antibodies. FACS analysis and immunogold labeling showed that the polyclonal anti-rVpFimH antibodies were able to recognize the FimH on V. parahaemolyticus cells. In vivo challenge of the rVpFimH-immunized mice with 2×LD50 dose of live bacteria showed one hundred percent survival. Thus, our findings clearly demonstrate the potential of FimH as an effective vaccine candidate against V. parahaemolyticus.
Assuntos
Adesinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Proteínas de Fímbrias/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Vibrioses/prevenção & controle , Vibrio parahaemolyticus/imunologia , Adesinas Bacterianas/genética , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Biofilmes/crescimento & desenvolvimento , Modelos Animais de Doenças , Proteínas de Fímbrias/genética , Doenças Transmitidas por Alimentos/microbiologia , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Alimentos Crus/microbiologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Alimentos Marinhos/microbiologia , Vibrioses/imunologia , Vibrio parahaemolyticus/genética , Virulência , Fatores de Virulência/genética , Fatores de Virulência/imunologiaRESUMO
BACKGROUND: Periostin has been shown to be upregulated in chronic rhinosinusitis with nasal polyps (CRSwNP), especially in the CRSwNP patients with asthma. However, the underlying mechanism that how periostin contributes to the polyp genesis remains unclear. METHODS: In this study, we collected 63 CRSwNP patients' nasal polyps (NPs) and 25 control subjects' uncinated tissues. The expressions of periostin, thymic stromal lymphopoietin (TSLP), and other proinflammatory cytokines were examined using IHC staining, qRT-PCR, Western blot (WB), ELISA and FACS. The eosinophil infiltration, phenotype profiles and clinical characteristics of 2 NP subtypes (eosinophilic and non-eosinophilic) were evaluated. We examined the effects and mechanisms of periostin on human nasal epithelial cells cultured at air-liquid interface (ALI). RESULTS: The expressions of periostin in NPs with asthma were higher than without asthma and the control nasal mucosa and positively associated with the TSLP (P<0.05). And the periostin levels was positively associated with the basement membrane thickness, goblet cell hyperplasia and tissue eosinophilia polyp tissues, as well as the clinical parameters (computed tomography scores, polyp size, and polyp recurrence after endoscopic surgery). In vitro experiments show that type 2 T-helper (Th2) cytokines interleukin-4 (IL-4), IL-13 and TGF-ß1 stimulates epithelial cells derived from polyp tissues to produce periostin through ERK and STAT6 signal pathways (P<0.05). Autocrine or recombinant periostin activates epithelial cells to produce TSLP via NF-κB signal pathways (P<0.05). The supernatant of periostin-treated epithelial cells activates dendritic cells (DCs), which subsequently induce naïve T cells to differentiate into Th2 cells and express IL-4 and IL-13. CONCLUSIONS: Our findings indicate periostin may play an important role in the polyp genesis, which can be considered as a therapeutic target for the management of CRSwNP.
RESUMO
Human papillomavirus (HPV) infection is a frequent cause of malignant and non-malignant disease, in particular among persons with HIV. HPV serotype-specific anti L1 antibodies protect against HPV infection but little is known about prophylactic HPV vaccine-induced cell-mediated immunity against HPV in high-risk individuals. We recently showed that both HPV vaccines (Gardasil® and Cervarix®) induce solid, serological immune responses in HIV-infected persons. This study aimed to characterize HPV-specific CD4 T cells in HIV-infected HPV-vaccine recipients, T cell responses being critical for B cell activation and antibody-isotype switching. Thirty HIV-infected patients on long-term antiretroviral treatment (ART) received 3 doses of either Cervarix (n = 15) or Gardasil (n = 15) vaccine at month 0, 1.5 and 6. Cryopreserved peripheral blood mononuclear cells (PBMC) from baseline, 7 and 12 months were subjected to 24-hour stimulation with specific pools of HPV L1-peptides (HPV6, 11, 16, 18, 31 and 45) and HPV E6/E7-peptide pools (HPV6/11 and HPV16/18). Fluorescence-activated cell sorting with intracellular staining (IC-FACS) against CD4, CD154, IL-2, and IFNγ was performed. Frequencies (%) of HPV-antigen specific CD4+ T cells (CD154+/IL-2+ or CD154+/ IFNγ+) were determined. Both HPV-vaccines significantly and comparably enhanced cell-mediated vaccine L1 antigen-specific immunity in HIV-positive adults receiving ART therapy at month 7 and 12 after first vaccine dose. This suggests that the vaccines induce CD4 T cellular memory despite HIV-induced immune compromisation.
Assuntos
Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Imunogenicidade da Vacina/imunologia , Vacinas contra Papillomavirus/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Método Duplo-Cego , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 system contribute to the initiation and development of Th2 responses. This study aimed to explore the involvement of TSLP, IL-25, IL-33, and their receptors in type 2 T-helper (Th) responses in chronic rhinosinusitis with nasal polyps (CRSwNPs) and their cross-regulation in human nasal epithelial cells (HNECs). METHODS: Immunohistochemistry, quantitative RT-PCR, ELISA, Bio-Plex assay, and flow cytometry were used to detect the expression of TSLP/common γ-like TSLP receptor (TSLPR)/IL-7 receptor α (IL-7Rα), IL-25/IL-17B receptor (IL-17RB), and IL-33/membrane-bound ST2 (ST2L)/soluble ST2 (sST2) in sinonasal mucosa and HNECs. HNECs cultured at an air-liquid interface were used to explore the expression in regulation of these cytokine systems. RESULTS: Compared with controls and noneosinophilic CRSwNP, the expression of TSLP/TSLPR/IL-7Rα and ST2L/sST2 was significantly increased in eosinophilic CRSwNP, predominantly in epithelial cells. In contrast, the expression of IL-33 and IL-25/IL-17RB was enhanced in epithelial cells in both eosinophilic and noneosinophilic CRSwNP compared to controls. The expression of TSLP, TSLPR, and ST2L was positively correlated with symptom and computer tomography scan scores in eosinophilic CRSwNP and with Th2 cytokine expression in sinonasal mucosa. The expression of ST2L was correlated with TSLP and its receptor expression. TSLP could induce ST2L expression that promoted IL-33-induced TSLP expression in HNECs. In addition, TSLP/TSLPR/IL-7Rα and ST2L could be induced by Th2 cytokines, while IL-25/IL-17RB and IL-33 could be upregulated by Th1/Th17 cytokines, in HNECs. CONCLUSIONS: The positive feedback loop between TSLP, IL-33 and their receptors, and Th2 cytokines may facilitate Th2-skewed inflammation in eosinophilic CRSwNP.
Assuntos
Citocinas/metabolismo , Células Epiteliais/metabolismo , Interleucina-33/metabolismo , Pólipos Nasais/metabolismo , Receptores de Citocinas/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imunomodulação , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/diagnóstico , Pólipos Nasais/imunologia , Ligação Proteica , Receptores de Superfície Celular/metabolismo , Receptores de Interleucina-7/metabolismo , Rinite/diagnóstico , Rinite/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Sinusite/diagnóstico , Sinusite/imunologia , Células Th2/imunologia , Células Th2/metabolismo , Receptores Toll-Like/agonistas , Adulto Jovem , Linfopoietina do Estroma do TimoRESUMO
CONTEXT: Exercise increases the levels of circulating inflammatory mediators. OBJECTIVE: Does an acute bout of exercise affect the mRNA gene expression level of inflammatory markers in peripheral blood mononuclear cells (PBMCs) and contribute to the circulating levels of inflammatory mediators? MATERIALS AND METHODS: Ten healthy, non-smoking men (22-28 years old) performed 1-hour cycling at 70% of VO2 max. RESULTS: The gene transcripts of CXCL16, IL-1ß, IL-8, COX-2, TXB21 and GATA3 were significantly up-regulated in PBMCs. Serum levels of CXCL16, IL-6, TNFα and IL-10 were also significantly increased after exercise. DISCUSSION AND CONCLUSION: Increased mRNA transcription of inflammatory genes in PBMCs may contribute to increased level of inflammatory markers after an acute bout of exercise. The increased mRNA levels of GATA-3 and TXB21 may indicate that T cell lymphocytes are activated and secrete cytokines into the circulation. It needs to be further investigated if exercise changes the Th1/Th2 balance.
Assuntos
Exercício Físico , Inflamação/sangue , Monócitos/metabolismo , Adulto , Biomarcadores/sangue , Células Cultivadas , Humanos , Masculino , Adulto JovemRESUMO
Complement is undeniably quintessential for innate immunity by detecting and eliminating infectious microorganisms. Recent work, however, highlights an equally profound impact of complement on the induction and regulation of a wide range of immune cells. In particular, the complement regulator CD46 emerges as a key sensor of immune activation and a vital modulator of adaptive immunity. In this review, we summarize the current knowledge of CD46-mediated signalling events and their functional consequences on immune-competent cells with a specific focus on those in CD4(+) T cells. We will also discuss the promises and challenges that potential therapeutic modulation of CD46 may hold and pose.