• Title/Summary/Keyword: Protective immunity

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A Moonlighting Protein Secreted by a Nasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections

  • Gwanghee Kim;Yoojin Lee;Jin Sun You;Wontae Hwang;Jeewon Hwang;Hwa Young Kim;Jieun Kim;Ara Jo;In ho Park;Mohammed Ali;Jongsun Kim;Jeon-Soo Shin;Ho-Keun Kwon;Hyun Jik Kim;Sang Sun Yoon
    • IMMUNE NETWORK
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    • v.23 no.4
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    • pp.31.1-31.18
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    • 2023
  • Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

Immunization of mice with chimeric protein-loaded aluminum hydroxide and selenium nanoparticles induces reduction of Brucella melitensis infection in mice

  • Tahereh Goudarzi;Morteza Abkar;Zahra Zamanzadeh;Mahdi Fasihi-Ramandi
    • Clinical and Experimental Vaccine Research
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    • v.12 no.4
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    • pp.304-312
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    • 2023
  • Purpose: Due to the many problems with commercially available vaccines, the production of effective vaccines against brucellosis is a necessity. The aim of this study was to evaluate the immune responses caused by the chimeric protein consisting of trigger factor, Bp26, and Omp31 (TBO) along with aluminum hydroxide (AH/TBO) and selenium (Se/TBO) nanoparticles (NPs) as adjuvants in mouse model. Materials and Methods: Recombinant antigen expression was induced in Escherichia coli BL21 (DE3) bacteria using IPTG (isopropyl-d-1-thiogalactopyranoside). Purification and characterization of recombinant protein was conducted through NiFe3O4 NPs, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blot. NP characteristics, including morphology and particle size, were measured in vitro. The recombinant TBO was loaded on to AH and Se NPs and were administered subcutaneously. After mice immunization, measurement of antibody titter and protection assay was performed. Results: The average sizes of AH and Se NPs were about 60 nm and 150 nm, respectively. The enzyme-linked immunosorbent assay results showed that the serum of mice immunized by subcutaneous injection with both nanovaccines produced significant immunoglobulin G (IgG) responses against the chimeric antigen. The results of TBO-specific IgG isotype (IgG2a/IgG1) analysis showed that both AH and Se NPs induced a type to T-helper immune response. In addition, the results of the challenge with the pathogenic strain of Brucella melitensis 16M showed that vaccinated mice with AH/TBO NPs indicated a higher reduction of bacterial culture than immunized mice with Se/TBO NPs and TBO alone. Conclusion: The results showed that AH NPs carrying chimeric antigen can be a promising vaccine candidate against brucellosis by producing protective immunity.

Efficacy of Genetic Adjuvant (Plasmid-Expressed Chicken Interleukin-6) and Chemical Adjuvant (Levamisole) on the Protective Immunity of Genetic Vaccine against Infectious Bursal Disease Virus (닭의 전염성 F낭병 바이러스 유전자백신에 의한 방어 면역에 Genetic Adjuvant (Chicken Interleukin-6)와 Chemical Adjuvant (Levamisole)의 효과)

  • Park, Jeong-Ho;Sung, Haan-Woo;Yoon, Byung-Il;Pak, Son-Il;Kwon, Hyuk-Moo
    • Korean Journal of Microbiology
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    • v.45 no.2
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    • pp.91-98
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    • 2009
  • Infectious bursal disease (IBD) caused by the infectious bursal disease virus (IBDV) has an important economic impact on the poultry industry worldwide. This study examined the adjuvant effects of a plasmid encoding chicken interleukin-6 (pcDNA-ChIL-6) and levamisole (LMS) on in ovo prime-boost vaccination using a genetic vaccine (pcDNA-VP243) to prime in chicken followed by a killed-vaccine boost. A pcDNA-VP243 was injected into the amniotic sac alone or in combination with a pcDNA-ChIL-6 or LMS at embryonation day 18, followed by an intramuscular injection of killed IBD vaccine at 1 week of age. The chicken were orally challenged with very virulent IBDV (vvIBDV) strain at 3 weeks of age and observed for 10 days. No mortality was observed in the groups that received the pcDNA-VP243 alone and pcDNA-VP243 plus pcDNA-ChIL-6 or LMS compared to 100% mortality in unvaccinated challenge control group. However, as determined by bursal damage (the presence of IBDV RNA, B/B ratio, and lesion score), a pcDNA-VP243 alone group was superior to pcDNA-VP243 plus pcDNA-ChIL-6 or LMS groups in the protection against post-challenge. These findings suggest that in ovo priming with genetic vaccine and boosting with killed vaccine is an effective strategy for protecting chicken against vvIBDV and the addition of pcDNA-ChIL-6 or LMS did not enhance protective immunity.

Evaluation of the Cell-Mediated Immunity in Treatment Failure Pulmonary Tuberculosis (치료실패 폐결핵 환자의 세포성면역반응에 관한 연구)

  • Park, Jeong-Kyu;Park, Jang-Seo;Kim, Hwa-Jung;Jo, Eun-Gyeong;Min, Dul-Lel;Lim, Jae-Hyun;Suhr, Ji-Won;Paik, Tae-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.1
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    • pp.13-25
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    • 1999
  • Background: Ineffective cell-mediated immune response in human tuberculosis is associated with a depressed Thl cytokine response and reduced production of IFN-$\gamma$. Most persons infected with Mycobacterium tuberculosis are healthy tuberculin reactors with protective immunity, but a minority with ineffective immunity develop extensive pulmonary tuberculosis. The cell-mediated immune response is an important aspect of host resistance to mycobacterial infection and is believed to be tightly regulated by a balance between Th1 cytokines including IFN-$\gamma$, IL-12, IL-18, regulated on activation, normal T cell expressed and secreted (RANTES) and Th2 counterparts such as IL-4, monocyte chemoattractant protein-l (MCP-l). Methods: Proliferation and mRNA expression of IFN-$\gamma$, RANTES and MCP-l by RT-PCR in peripheral blood mononuclear cells (PBMCs) in response to in vitro stimulation with mycobacterial antigens were compared in pulmonary tuberculosis patients with cured and treatment failure and in tuberculin-positive and tuberculin-negative healthy subjects. Results: Defective proliferative responsiveness to aqueous TSP antigen was involved with treatment failure tuberculosis patients. Aqueous TSP antigen-induced IFN-$\gamma$ and RANTES mRNA expression was decreased in treatment failure tuberculosis patients compared with healthy tuberculin reactors and cured tuberculosis patients (23.1 % versus 90.0% for IFN-$\gamma$ and 46.2% versus 70.0% versus 46.2% for RANTES). The frequency of MCP-l mRNA expression to aqueous TSP antigen in treatment failure tuberculosis patients was greater than in healthy tuberculin reactors and cured tuberculosis patients (76.9% versus 40.0%). Conclusion: The increasing expression of MCP-1 mRNA in response to aqueous TSP antigen might be predicted to favor Th1 responses and restricted Th1 responses in treatment failure of pulmonary tuberculosis.

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Evaluation of Antibodies Against Haemophilus influenzae Type b in Korean Adults (우리나라 성인에서 Haemophilus influenzae type b에 대한 항체 평가)

  • Lee, Ji Hyen;Kim, Han Wool;Lee, Soyoung;Kim, Kyung-Hyo
    • Pediatric Infection and Vaccine
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    • v.24 no.3
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    • pp.125-133
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    • 2017
  • Purpose: After the introduction of Haemophilus influenzae type b (Hib) vaccine in 1995 in Korea, it was included in the national immunization program in 2013. In the post-Hib vaccine era, some studies in other countries reported that invasive Hib disease affects adults, especially the elderly and immunocompromised persons, more often than it affects children. To evaluate disease susceptibility, quantitative and qualitative analysis of anti-polyribosylribitol phosphate (PRP) antibodies were carried out in Korean adults aged 20 to 85 years. Methods: Sera were collected from 39 healthy adults (20 to 50 years of age) and from 30 elderly adults (75 to 85 years of age) who did not have immune-compromising conditions. The concentration of anti-PRP immunoglobulin G (IgG) and serum bactericidal indices (SBIs) were measured by enzyme-linked immunosorbent assay and serum bactericidal assay. Results: Geometric mean concentrations of anti-PRP IgG and geometric mean SBIs were $0.88{\mu}g/mL$ (95% confidence interval [CI], 0.17 to 3.85) and 354 (95% CI, 50 to 2,499) in young adults and $1.67{\mu}g/mL$ (95% CI, 0.53 to 5.24) and 449 (95% CI, 146 to 1,376) in elderly adults, respectively. When the threshold of seropositivity for anti-PRP IgG was applied as 0.15 or $1.0{\mu}g/mL$, which is the protective antibody level in children, seropositive rates were 87.2% or 53.8% in young adults and 100% or 60% in elderly adults. The seropositivity rates of the SBI ($SBI{\geq}4$) were 82.1% and 100% in the groups, respectively. Conclusions: Most subjects in the adult and elderly adult groups display immunity to Hib based on quantitative and qualitative antibody levels, but not all. Because high immunization and low Hib circulation rates may reduce the natural Hib immunity in the population, monitoring Hib immunity as well as disease are needed continuously.

The Purification and Immunogenicity of TB-14 Recombinant Protein of Mycobacterium tuberculosis (결핵균 특이 TB-14 재조합 단백질의 분리 및 세포성 면역반응에 미치는 영향)

  • Song, Ho-Yeon;Kim, Young-Hee;Kim, Chang-Hwan;Min, Young-Ki;Kim, Dae-Joong;Ko, Kwang-Kjune
    • Tuberculosis and Respiratory Diseases
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    • v.61 no.3
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    • pp.239-247
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    • 2006
  • Background: Culture filtrate proteins secreted by mycobacteria are thought to play an important role in inducing protective immunity and to develop new methods for diagnosing tuberculosis. Methods: A culture filtrate protein of M. avium that was strongly reactive with goat antiserum against M. intracellulare was constructed. Its homologous protein (TB-14) in M. tuberculosis was cloned, expressed and purified. The inductions of IFN-${\gamma}$ stimulated with $10{\mu}g$ of TB-14 recombinant protein and $10{\mu}g$ PPD were estimated by using whole bloods from seven PPD (-) subjects, seven PPD (+) healthy volunteers and nine tuberculosis patients. Results: M. avium culture filtrate protein was confirmed as a hypothetical protein that was termed contig 116. A novel 14-kDa recombinant protein (TB-14) of M. tuberculosis was composed of 148 amino acids, including 30 amino acids of the signal peptide, and it showed 78% homology with M. avium. In the PPD (+) healthy volunteers, recombinant TB-14 protein strongly induced the secretion of IFN-${\gamma}$ in whole blood cultures. Conclusion: These results suggest that TB-14 recombinant protein might play an important role in inducing cell-mediated immunity against tuberculosis. Furthermore, TB-14 protein antigen and its antiserum will be available for the development of new diagnostic tools for tuberculosis.

Effects of garlic Allium sativum on the immune responses of olive flounder Paralichthys olivaceus (마늘, Allium sativum이 넙치, Paralichthys olivaceus의 면역반응에 미치는 영향)

  • Lee, Jun-Hee;Woo, Sung-Ho;Eom, Yong-Hwan;Hwang, Bun-Ok;Kwon, Mun-Gyeong;Bang, Jong-Deuk;Park, Soo-Il
    • Journal of fish pathology
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    • v.23 no.1
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    • pp.69-83
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    • 2010
  • This study was aimed to investigate the effects of injection of garlic, Allium sativum, extract and immersion in garlic juice on the nonspecific immunity and the resistance against the artificial infection of Streptococcus iniae and Edwardsiella tarda of the olive flounder, Paralichthys olivaceus. The nonspecific immune mechanisms were assessed in terms of lysozyme activity, nitroblue-tetrazolium (NBT) assay and superoxide dismutase (SOD) activity etc. Relative percent survival (RPS) was assessed by the challenge with S. iniae BS10 or E. tarda KE-1. Almost of the garlic extract injected groups showed the enhanced level of the tested nonspecific immune factors. In the challenge test with S. iniae and E. tarda, RPS of 5% garlic extract pre-injected group was much higher than that of any other tested groups, respectively. Almost of the garlic juice immersion tested groups exhibited strengthened nonspecific immune defence factors, lysozyme activity, the number of lymphocytes and neutrophils, NBT reduction and SOD activity in kidney. In the challenge with S. iniae and E. tarda, RPS in the 0.25 g/L of garlic juice immersed group was much higher than any other tested groups, respectively. The results suggest that the garlic extract and juice would be effective to enhance the nonspecific immunity and protective ability of olive flounder against fish disease such as S. iniae and E. tarda.

Induction of Systemic and Mucosal Immune Responses in Mice Orally Administered with Recombinant Attenuated Salmonella Expressing Subunits of P Fimbriae of Avian Pathogenic Escherichia coli (마우스에서 조류 병원성 대장균의 P Fimbriae subunits을 발현하는 약독화 살모넬라균 경구 접종 후 면역 반응 유도 실험)

  • Oh, In-Gyeong;Moon, Bo-Mi;Lee, John-Hwa;Hur, Jin
    • Journal of Veterinary Clinics
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    • v.28 no.3
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    • pp.297-302
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    • 2011
  • Avian pathogenic Escherichia coli (APEC) causes a number of extraintestinal diseases in poultry. A virulence factor, P-fimbriae is firmly associated with the diseases. In this study, to develop an effective vaccine for the prevention of APEC, recombinant attenuatted Salmonella Typhimurium vaccines expressing PapA and PapG of P-fimbriae were evaluated whether these induced protective immune responses in murine models. Female BALB/c mice were primed and boosted orally at 7 and 10 weeks of age. In all immunized mice, the antigen-specific serum IgG levels were remained higher than those in the control mice from the fourth week post inoculation till the end of this study. In addition, antigen-specific serum IgG levels in the prime-booster immunized mice were enhanced as compared to the single immunized mice among each immunized group. The antigen-specific mucosal IgA levels in the mice immunized with each strain also induced higher than those in control mice. In addition, serum IgG and fecal IgA levels in mice administered with the combination of both strains were highly induced compared to those in mice immunized with each strain alone. These results indicated that PapA and PapG worked together for inducing high immune responses. To partly discern the nature of immunity induced by the strains, we quantified serum IgG subtypes IgG1 and IgG2a specific to antigens. The PapA and PapG strains biased the immunity to the Th1-type, as determined by the IgG2a/IgG1 ratio. On the other hand, the immunization with the both strains in combination produced mixed Th1- and Th2-type immune responses. These indicated that immunization with the combination of PapA and PapG could elicit both humoral and cell-mediated immunities.

The Implementation Status of Dental Treatment Infection Control Standards of Dental Hygienists (치과위생사의 치과진료 감염방지기준에 관한 연구)

  • Yoo, Ha-Na;Kang, Kyung-Hee
    • Journal of Digital Convergence
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    • v.11 no.12
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    • pp.649-656
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    • 2013
  • This study was conducted to find out about the implementation status of dental treatment infection control standards of dental hygienists. The subjects of research were the dental hygienists working at dentist offices in Chungnam, Cheonan-si using self-input method from July 25th, 2012 to August 1st 2012. The collected data was analyzed after computerized statistical processing using SPSS 18.0. For hepatitis B vaccination, the results were high with 75.0% of answers being 'yes' or auto-active immunity, but for the latest hepatitis vaccination period showed highest results in '5 years or more ago' with 48.0%. Although 93.0% answered that vaccination was important, the percentage of replies that they had vaccination education was relatively low with 41.0%. For the use of personal protection tools the use of protective goggles was low compared to the use of masks and medical gloves. The percentage of subjects that answered that they always wash their hands before treatment was relatively low with 56.0% compared to 82.0% of subjects that answered that they always washed their hands after treatment. Dental treatment equipment washing before sterilization, use of packing and re-sterilization of tools with damaged packing showed high results for 'yes', but the ratio of subjects that answered 'no' to water line management was low with 39%.

CD40-CD40 Ligand Interactions in the Production of IL-12 and IFN-γ by Tuberculous Pleural Mononuclear Cells

  • Song, Chang-Hwa;Nam, Hyun-Hee;An, Jeun-Ok;Lee, Ji-Sook;Kim, Hwa-Jung;Park, Jeong-Kyu;Suhr, Ji-Won;Jung, Sung-Soo;Na, Moon-Jun;Paik, Tae-Hyun;Jo, Eun-Kyeong
    • IMMUNE NETWORK
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    • v.2 no.3
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    • pp.142-149
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    • 2002
  • Background: Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more $IFN-{\gamma}$ (10- to 70-fold) after in vitro PPD stimulation than freshly isolated pleural cells from malignant pleurisy. The present study was designed to determine whether blocking the CD40-CD40 ligand (CD40L) interaction decreases $IFN-{\gamma}$ production by altering IL-12 levels. Methods: IL-12 and $IFN-{\gamma}$ production after neutralizing anti-CD40L antibody treatment was compared to the efficacy of anti-CD80, anti-CD86, and a combination of anti-CD80 and CD86 (CD80+86) monoclonal antibodies (mAb). These activities were measured by enzyme-linked immunosorbent assays (ELISAs) and reverse transcription-polymerase chain reaction (RT-PCR), after in vitro stimulation with PPO antigen (Ag). Results: Neutralization of CD80, CD86 and CD80+86 did not decrease $IFN-{\gamma}$ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and $IFN-{\gamma}$. In addition, neutralization of CD40L completely inhibited IL-12 p40 and $IFN-{\gamma}$ mRNA expression. Conclusion: The CD40-CD40L interaction might play a major role in IL-12 and $IFN-{\gamma}$ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.