BMC Immunology

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Immunomodulation of human monocytes following exposure to Lutzomyia intermedia saliva
BMC Immunology - Tập 9 - Trang 1-8 - 2008
Maria José Menezes, Dirceu J Costa, Jorge Clarêncio, José Carlos Miranda, Aldina Barral, Manoel Barral-Netto, Cláudia Brodskyn, Camila I de Oliveira
Sand fly saliva contains potent and complex pharmacologic molecules that are able to modulate the host's hemostatic, inflammatory, and immune systems. In this study, we evaluated the effects of salivary gland sonicate (SGS) of Lutzomyia intermedia, the natural vector of Leishmania braziliensis, on monocytes obtained from the peripheral blood mononuclear cells (PBMC) of healthy volunteers. We investigated the effects of sand fly saliva on cytokine production and surface molecule expression of LPS-stimulated human monocytes uninfected or infected with L. braziliensis. Pre-treatment of non-infected human monocytes with L. intermedia SGS followed by LPS-stimulation led to a significant decrease in IL-10 production accompanied by a significant increase in CD86, CD80, and HLA-DR expression. Pre-treatment with SGS followed by LPS stimulation and L. braziliensis infection led to a significant increase in TNF-α, IL-6, and IL-8 production without significant alterations in co-stimulatory molecule expression. However, pre-treatment with L. intermedia SGS did not result in significant changes in the infection rate of human monocytes. Our data indicate that L. intermedia saliva is able to modulate monocyte response, and, although this modulation is dissociated from enhanced infection with L. braziliensis, it may be associated with successful parasitism.
Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in a rat stroke model
BMC Immunology - Tập 16 - Trang 1-7 - 2015
Martin Juenemann, Tobias Braun, Simone Doenges, Max Nedelmann, Clemens Mueller, Georg Bachmann, Pratibha Singh, Franz Blaes, Tibo Gerriets, Marlene Tschernatsch
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke. Sixteen male Wistar rats were randomized into two groups twice receiving either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30 minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted MRI was carried out 24 hours after MCAO. MRI-examination showed a significant increase of infarct size in relation to the cerebral hemisphere volume with NMO-IgG treated animals (27.1% ± 11.1% vs. 14.3% ± 7.2%; p < 0.05) when corrected for the space-occupying effect of vasogenic edema formation and similar results without edema correction (34.4% ± 16.4% vs. 17.5% ± 9.3%; p < 0.05). Furthermore, T2-RT revealed a significant increase in cortical brain water content of the treatment group (19.5 ms ± 9.7 ms vs. 9.2 ms ± 5.2 ms; p < 0.05). These results support the functional impact of NMO-antibodies and also offer an in-vivo-applicable animal model to investigate the properties of AQP4 in ischemic stroke.
Anti-inflammatory protein TNFα-stimulated gene-6 (TSG-6) reduces inflammatory response after brain injury in mice
BMC Immunology - Tập 22 Số 1
Kazadi Nadine Mutoji, Mingxia Sun, Amanda Nash, Sudan Puri, Vincent C. Hascall, Vivien Jane Coulson‐Thomas
Abstract Background

Current research suggests that the glial scar surrounding penetrating brain injuries is instrumental in preserving the surrounding uninjured tissue by limiting the inflammatory response to the injury site. We recently showed that tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), a well-established anti-inflammatory molecule, is present within the glial scar. In the present study we investigated the role of TSG-6 within the glial scar using TSG-6 null and littermate control mice subjected to penetrating brain injuries.

Results

Our findings show that mice lacking TSG-6 present a more severe inflammatory response after injury, which was correlated with an enlarged area of astrogliosis beyond the injury site.

Conclusion

Our data provides evidence that TSG-6 has an anti-inflammatory role within the glial scar.

In vitro production of peroxynitrite by haemocytes from marine bivalves: C-ELISA determination of 3-nitrotyrosine level in plasma proteins from Mytilus galloprovincialis and Crassostrea gigas
BMC Immunology - Tập 2 - Trang 1-5 - 2001
Jean Torreilles, Bernard Romestand
Peroxynitrite is increasingly proposed as a contributor to defence system in marine bivalve. It can be formed by combinaison of superoxide and nitric oxide, and can react with tyrosine residues of proteins giving rise to 3-nitrotyrosine. The present article describes a competitive ELISA for the measurement of 3-nitrotyrosine contents of plasma proteins from marine bivalves by means of a monoclonal anti 3-nitrotyrosine antibody mouse IgG. This assay is sensitive enough to determine the amounts of 3-nitrotyrosine in plasma proteins from one animal only. Using the C-ELISA, we have shown that the phagocytosis of zymosan particles increased the 3-nitrotyrosine levels of plasma proteins from mussel M. galloprovincialis and oyster C. gigas 5.8 and 7.5 times respectively.
The role of Toll-like receptor-4 in pertussis vaccine-induced immunity
BMC Immunology - Tập 9 - Trang 1-15 - 2008
Sander Banus, Rachel M Stenger, Eric R Gremmer, Jan AMA Dormans, Frits R Mooi, Tjeerd G Kimman, Rob J Vandebriel
The gram-negative bacterium Bordetella pertussis is an important causative agent of pertussis, an infectious disease of the respiratory tract. After introduction of whole-cell vaccines (wP) in the 1950's, pertussis incidence has decreased significantly. Because wP were found to be reactogenic, in most developed countries they have been replaced by acellular vaccines (aP). We have previously shown a role for Toll-like receptor 4 (Tlr4) in pertussis-infected mice and the pertussis toxin (Ptx)-IgG response in wP-vaccinated children, raising the issue of the relative importance of Tlr4 in wP vaccination of mice. Here we analyze the effects of wP and aP vaccination and B. pertussis challenge, in Tlr4-deficient C3H/HeJ and wild-type C3H/HeOuJ mice. aP consists of Ptx, filamentous hemagglutinin (FHA), and pertactin (Prn). We show an important role of Tlr4 in wP and (to a lesser extent) aP vaccination, induction of Th1 and Th17 cells by wP but not aP vaccination, and induction of Th17 cells by infection, confirming data by Higgins et al. (J Immunol 2006, 177: 7980–9). Furthermore, in Tlr4-deficient mice, compared to wild-type controls (i) after vaccination only, Ptx-IgG (that was induced by aP but not wP vaccination), FHA-IgG, and Prn-IgG levels were similar, (ii) after infection (only), lung IL-1α and IL-1β expression were lower, (iii) after wP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while lung IL-1β, TNF-α, IFN-γ, IL-17, and IL-23 expression were lower, and lung pathology was absent, and (iv) after aP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while Ptx-IgG level was lower. Tlr4 does not influence the humoral response to vaccination (without challenge), plays an important role in natural immunity, wP and aP efficacy, and induction of Th1 and Th17 responses, is critical for lung pathology and enhances pro-inflammatory cytokine production after wP vaccination and challenge, and diminishes Th2 responses after both wP and aP vaccination and challenge. wP vaccination does not induce Ptx-IgG. A role for LPS in the efficacy of wP underlines the usefulness of LPS analogs to improve bacterial subunit vaccines such as aP.
Đánh giá cân nặng và chiều cao của bệnh nhân mắc các rối loạn suy giảm miễn dịch nguyên phát và nhóm trẻ em mắc các bệnh nhiễm trùng đường hô hấp tái phát Dịch bởi AI
BMC Immunology - Tập 21 - Trang 1-10 - 2020
Karolina Pieniawska-Śmiech, Kamil Bar, Mateusz Babicki, Karol Śmiech, Aleksandra Lewandowicz-Uszyńska
Suy giảm miễn dịch nguyên phát (PID) là một nhóm các rối loạn mãn tính nghiêm trọng trong đó phản ứng miễn dịch là không đủ. Do đó, điều này dẫn đến việc tăng nguy cơ mắc các bệnh nhiễm trùng. Tính đến nay, có khoảng 350 rối loạn khác nhau được phân loại trong nhóm này. Cũng có những bệnh nhân bị nhiễm trùng đường hô hấp tái phát (RRTI), tuy nhiên nhóm này không cho thấy bất kỳ bất thường nào liên quan đến các xét nghiệm miễn dịch đã thực hiện. Nhiều yếu tố, bao gồm cả y học, có thể ảnh hưởng đến sự phát triển thể chất của một đứa trẻ. Dữ liệu như cân nặng và chiều dài khi sinh, cùng với cân nặng, chiều cao, BMI trong thời gian nhập viện đã được thu thập từ hồ sơ y tế của 195 bệnh nhân trong thời gian họ điều trị tại Khoa Miễn dịch lâm sàng và Nhi khoa của Bệnh viện J. Gromkowski ở Wrocław. Các nhóm được nghiên cứu bao gồm bệnh nhân mắc PID, RRTI và một nhóm đối chứng là trẻ em khỏe mạnh. Mục tiêu của chúng tôi là đánh giá sự phát triển thể chất của trẻ em mắc PID và trẻ em mắc RRTI thông qua việc đánh giá chiều cao và cân nặng của chúng. Tất cả các tham số đều được đánh giá bằng cách sử dụng biểu đồ phần trăm, phù hợp nhất cho dân số Ba Lan. Cân nặng và chiều cao trung bình thấp nhất được phát hiện ở nhóm bệnh nhân PID. Trẻ em mắc PID trong thời gian nhập viện có cân nặng trung bình thấp hơn có ý nghĩa thống kê so với nhóm đối chứng và gần 18% trong số họ có chiều cao nằm dưới phần trăm thứ 3. Sự khác biệt có ý nghĩa thống kê đã được phát hiện giữa họ và nhóm RRTI về mặt cân nặng, chiều cao và tình trạng dinh dưỡng. Sự khác biệt có ý nghĩa thống kê được phát hiện giữa tình trạng dinh dưỡng của nhóm PID và nhóm đối chứng. Có tỷ lệ bệnh nhân PID mắc các rối loạn phát triển thể chất cao hơn so với trẻ em khỏe mạnh. Những phát hiện của chúng tôi chỉ ra rằng cần phải tiếp tục điều tra các bất thường của hệ miễn dịch và ảnh hưởng của nó đến sự phát triển thể chất của trẻ em.
#suy giảm miễn dịch nguyên phát #trẻ em #điều tra #phát triển thể chất #nhiễm trùng đường hô hấp
Pathogen exposure influences immune parameters around weaning in pigs reared in commercial farms
BMC Immunology - Tập 23 Số 1
Julie Hervé, Karine Haurogné, Arnaud Buchet, Elodie Bacou, Grégoire Mignot, Marie Allard, Mily Leblanc-Maridor, Solenn Gavaud, Anne Lehébel, Elena Terenina, Pierre Mormède, Élodie Merlot, Catherine Belloc, Jean-Marie Bach, Blandine Lieubeau
Abstract Background

Multiple antigenic stimulations are crucial to immune system training during early post-natal life. These stimulations can be either due to commensals, which accounts for the acquisition and maintenance of tolerance, or to pathogens, which triggers immunity. In pig, only few works previously explored the influence of natural exposition to pathogens upon immune competence. We propose herein the results of a multicentric, field study, conducted on 265 piglets exposed to contrasted pathogen levels in their living environment. Piglets were housed in 15 different commercial farms, sorted in two groups, low (HSLOW)- and high (HSHIGH)-health status farms, depending on their recurrent exposition to five common swine pathogens.

Results

Using animal-based measures, we compared the immune competence and growth performances of HSLOW and HSHIGH pigs around weaning. As expected, we observed a rise in the number of circulating leucocytes with age, which affected different cell populations. Monocyte, antigen-experienced and cytotoxic lymphocyte subpopulation counts were higher in piglets reared in HSLOW farms as compared to their HSHIGH homologs. Also, the age-dependent evolution in γδ T cell and neutrophil counts was significantly affected by the health status. With age, circulating IFNα level decreased and IgM level increased while being greater in HSLOW piglets at any time. After weaning, LPS-stimulated blood cells derived from HSLOW piglets were more prone to secrete IL-8 than those derived from HSHIGH pigs did. Monocytes and granulocytes issued from HSLOW pigs also exhibited comparable phagocytosis capacity. Altogether our data emphasize the more robust immunophenotype of HSLOW piglets. Finally, piglets raised under higher pathogen pressure grew less than HSHIGH piglets did and exhibited a different metabolic profile. The higher cost of the immune responses associated with the low farm health status may account for lower HSLOW piglet performances.

Conclusions

Altogether, our data, obtained in field conditions, provide evidence that early exposure to pathogens shapes the immune competence of piglets. They also document the negative impact of an overstimulation of the immune system on piglets’ growth.

Reversing BCG-mediated autophagy inhibition and mycobacterial survival to improve vaccine efficacy
BMC Immunology - Tập 23 - Trang 1-12 - 2022
Maria Gonzalez-Orozco, Emily J. Strong, Ruchi Paroha, Sunhee Lee
Autophagy is an important mechanism for promoting Mycobacterium clearance from macrophages. Pathogenic and non-pathogenic mycobacterium can activate the mTOR pathway while simultaneously inducing autophagy. M. tuberculosis and M. bovis BCG inhibit autophagy and favor intracellular bacteria survival. We observed that pre-infection of live or heat-killed BCG could prevent autophagy induced by pharmacological activators or M. smegmatis, a strong autophagy-inducing mycobacterium. BCG-derived lipids are responsible for autophagy inhibition. However, post-infection with BCG could not stop the autophagy initiated by M. smegmatis, which increases further autophagy induction and mycobacteria clearance. Coinfection with BCG and heat killed M. smegmatis enhanced antigen specific CD4+ T cell responses and reduced mycobacterial survival. These results suggest that autophagy-inducing M. smegmatis could be used to promote better innate and consequential adaptive immune responses, improving BCG vaccine efficacy.
NK cell predicts the severity of acute graft-versus-host disease in patients after allogeneic stem cell transplantation using antithymocyte globulin (ATG) in pretreatment scheme
BMC Immunology - Tập 20 - Trang 1-9 - 2019
Ping Zhang, Shujun Yang, Yujing Zou, Xiao Yan, Hao Wu, Miao Zhou, Yong Cheng Sun, Yi Zhang, Huiling Zhu, Kaihong Xu, Yi Wang, Li Xia Sheng, Qitian Mu, Liguang Sun, Guifang Ouyang
Graft-versus-host disease (GVHD) is one of the most complex complications after allogeneic stem cell transplantation. Current standard of grading system is based on clinical symptoms in skin, liver and intestinal. However, it’s difficult to differ GVHD and its extent just by clinical manifestation. Here we retrospectively analyzed cell immune function in patients implemented allogeneic stem cell transplantation in Ningbo first Hospital from Jan 2013 to Jan 2018. the data are collected from 51 patients (mean age was 42; 45.1% women). The average NK cell percentage was 39.31% in severe GVHD (Grade III-IV), was 16.98% in mild GVHD (GradeI-II), while was 21.15% in No GVHD group. The statistical analysis showed difference among each grade. Further analysis was performed in Antithymocyte globulin (ATG) treated group and control group. We showed NK Cell percentage was sharply different in ATG treated group: 47.34% in severe GVHD, 11.98% in mild GVHD group, while 18.3% in no GVHD group. However, in control group, the average percentage of NK cells was 23.27% in severe GVHD, was 23.22%in mild GVHD group, while was 21.13% in no GVHD group. The data supports that ATG can prevent GVHD by increasing NK cell percentage. The percentage of NK cell seemed to be a useful probe to evaluate the severity of GVHD in allogeneic stem cell transplantation patients using ATG in pretreatment.
Identification of adjuvants for clinical trials performed with Plasmodium falciparum AMA1 in rabbits
BMC Immunology - Tập 20 - Trang 1-12 - 2019
Sumera Younis, Bart W. Faber, Clemens H.M. Kocken, Edmond J. Remarque
In this study, seven adjuvants were compared for use with Plasmodium falciparum DiCo-Apical Membrane Antigen 1 (Pf-DiCo-AMA1), with the aim to identify an ideal adjuvant which yields high antibody titres and potentially broadens the responses in clinical trials. The following adjuvant formulations were evaluated: SE, SE-GLA, Liposomes, Liposomes-GLA, CoVaccine HT™, ImSaVac-P and ImSaVac-P o/w. The study was performed in rabbits, which were immunized with FVO-AMA1 in combination with one of the seven adjuvants. Antibody levels (humoral responses) and functional activity of the antibodies induced against malaria vaccine candidate AMA1 were evaluated. Thus, in this study the ideal adjuvant is expected to induce high functional antibody levels, a long-lived response, and a broad cross-strain activity. AMA1 formulated in all adjuvants was immunogenic. However, the magnitude of the immune responses differed between the seven adjuvants. The highest IgG levels were observed for the CoVaccine HT™ group, this was statistically significant for all four AMA1 variants versus all other adjuvant groups. No differences were observed in the breadth of the humoral response, i.e., increased recognition of AMA1 variants. Also, Growth Inhibition Activity (GIA) for both Plasmodium falciparum strains (FCR3 – homologous to FVO AMA1 protein and NF54 – heterologous to FVO AMA1 protein) were significantly higher in the CoVaccine HT™ group as compared to the other adjuvant groups. In brief, all seven vaccine – adjuvant formulations were immunogenic. The magnitude of the immune responses differed between the seven adjuvants. No statistically significant differences were observed in the breadth of the humoral response, nor in longevity of the response. Nevertheless, AMA1 formulated in CoVaccine HT™ appeared as the best adjuvant for use in clinical trials.
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