scholarly journals Galectins from Onchocerca ochengi and O. volvulus and their immune recognition by Wistar rats, Gudali zebu cattle and human hosts

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ngwafu Nancy Ngwasiri ◽  
Norbert W. Brattig ◽  
Dieudonné Ndjonka ◽  
Eva Liebau ◽  
Archile Paguem ◽  
...  

Abstract Background During the last two decades research on animal filarial parasites, especially Onchocerca ochengi, infecting cattle in savanna areas of Africa revealed that O. ochengi as an animal model has biological features that are similar to those of O. volvulus, the aetiological agent of human onchocerciasis. There is, however, a paucity of biochemical, immunological and pathological data for O. ochengi. Galectins can be generated by parasites and their hosts. They are multifunctional molecules affecting the interaction between filarial parasites and their mammalian hosts including immune responses. This study characterized O. ochengi galectin, verified its immunologenicity and established its immune reactivity and that of Onchocerca volvulus galectin. Results The phylogenetic analysis showed the high degree of identity between the identified O. ochengi and the O. volvulus galectin-1 (ß-galactoside-binding protein-1) consisting only in one exchange of alanine for serine. O. ochengi galectin induced IgG antibodies during 28 days after immunization of Wistar rats. IgG from O. ochengi-infected cattle and O. volvulus-infected humans cross-reacted with the corresponding galectins. Under the applied experimental conditions in a cell proliferation test, O. ochengi galectin failed to significantly stimulate peripheral blood mononuclear cells (PBMCs) from O. ochengi-infected cattle, regardless of their parasite load. Conclusion An O. ochengi galectin gene was identified and the recombinantly expressed protein was immunogenic. IgG from Onchocerca-infected humans and cattle showed similar cross-reaction with both respective galectins. The present findings reflect the phylogenetic relationship between the two parasites and endorse the appropriateness of the cattle O. ochengi model for O. volvulus infection research.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ngwafu Nancy Ngwasiri ◽  
Norbert W. Brattig ◽  
Dieudonné Ndjonka ◽  
Eva Liebau ◽  
Archile Paguem ◽  
...  

An amendment to this paper has been published and can be accessed via the original article.


Author(s):  
В.Н. Сахаров ◽  
П.Ф. Литвицкий ◽  
Е.И. Алексеева ◽  
Н.А. Маянский ◽  
Р.Ш. Закиров

Цель исследования - изучение перепрограммирования мононуклеарных лейкоцитов на модели системного ювенильного идиопатического артрита (сЮИА), воспроизводимой у крыс Wistar с использованием полного адъюванта Фрейнда и липополисахарида. Методика. сЮИА воспроизведен у 6-месячных крыс-самцов Wistar. На 40-е сут. эксперимента животные были разделены на 3 группы: 1-я группа - контроль; 2-я - группа доксициклина; 3-я - группа дексаметазона. Взятие проб крови у животных проводили на нулевые, 41-е и 55-е сут. Мононуклеарные клетки периферической крови выделяли гравиметрически, после чего окрашивали их на маркеры и внутриклеточные цитокины. Дифференцировали моноциты (CD3-CD4+) и Т-хелперы (CD3+CD4+). Анализировали динамику внутриклеточной экспрессии интерлейкина IL-4 (рассматривали как маркер про-М2 фенотипа, так как в случае выделения из клетки ИЛ-4 служит стимулятором М2 поляризации макрофагов) и IFN-g (как маркер про-М1 фенотипа) по данным проточной цитофлуориметрии. Применяли непараметрический статистический тест Mann-Whitney-Wilcoxon в программе R для статистической обработки данных. Результаты и заключение. При моделировании сЮИА выявлено закономерное изменение фенотипа моноцитов. Применение же доксициклина и дексаметазона приводило к более ранней поляризации их по про-М2-пути в отношении моноцитов (на 41-е сут.) в сравнении с контролем. Про-М1 эффект (на 55-е сут., в сравнении с контролем) выявлен также в группах доксициклина и дексаметазона. У животных разных групп обнаружены характерные динамические изменения внутриклеточной экспрессии цитокинов. Важно, что различная направленность поляризации фенотипа при сЮИА и применении препаратов наблюдается не только у моноцитов, но и у Т-хелперов. The study objective was to evaluate targeted reprogramming of peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis (sJIA) modeled in 6-month-old male Wistar rats by co-administration of complete Freund’s adjuvant and lipopolysaccharide. Methods. On day 40 of the experiment, rats were divided into three groups: control, doxycycline, and dexamethasone groups. Blood samples were collected on days 0, 41, and 55. Peripheral blood mononuclear cells were isolated gravimetrically and stained for markers and cytokines. Monocytes (CD3-CD4+) and T-helpers (CD3+CD4+) were differentiated as target cells. IL-4 was considered a marker for the pro-M2 phenotype since IL-4 can activate M2 macrophage polarization; IFN-g was considered a marker for the pro-M1 phenotype. Time-related changes in the intracellular expression of IL-4 and IFN-g were studied using flow cytometry. Data were analyzed using nonparametric statistical tests (Mann-Whitney-Wilcoxon) in the R environment for statistical computing. Results and conclusions. Monocytes (like macrophages) underwent reprogramming during the development of modeled sJIA disease. In monocytes of doxycycline and dexamethasone treatment groups, pro-M2 effects were observed earlier (day 41) than in the control group. Pro-M1 effects were observed in monocytes of doxycycline and dexamethasone groups on day 55, as compared with the control group. Characteristic time-related changes of intracellular cytokine expression were described for different groups. Importantly, the differently directed phenotype polarization was observed in sJIA and treatment groups for both monocytes and T-helpers.


1998 ◽  
Vol 4 (3) ◽  
pp. 143-146 ◽  
Author(s):  
Philippe Monteyne ◽  
Christian JM Sindic

Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the mRNA coding for different cytokines in peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) cells from 18 multiple sclerosis (MS) patients as compared with 21 other neurological patients. mRNA levels were quantitated by radioactive hybridization of the PCR products. Expression of tumor necrosis factor (TNF)-a, interferon (IFN)-g, and interleukin (IL)-10 mRNA was elevated in CSF cells of MS patients. In many MS patients, both proinflammatory and immunoregulatory cytokine messages were detected in the CSF compartment. Such immune reactivity of CSF cells, as opposed to PBMC, was not associated with higher clinical activity of the disease. Expression of the B7.1 accessory molecule mRNA was similarly investigated. In the CSF, it was detected only in some clinically active MS cases and in other inflammatory diseases.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17536-17536
Author(s):  
D. Decaudin ◽  
A. Subtil ◽  
A. Ferreri ◽  
A. Vincent-Salomon ◽  
M. Ponzoni ◽  
...  

17536 Background: A high prevalence of Chlamydia psittaci infection in both tumor tissues and peripheral blood mononuclear cells of Italian patients with OAL has been reported (Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell’Oro S, Fleischhauer K, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004;96(8):586–94.) This association has not been confirmed in some regions of the USA, and no data from other European countries are available. We therefore investigated the presence of DNA of C. psittaci, C. trachomatis, and C. pneumoniae DNA in French patients (pts) with OAL. Methods: Tumor samples from ophthalmologic biopsies of 16 OAL pts (10 conjunctiva, 6 orbit) were included in the study. Histologic type were MALT-type (n = 8), lymphoplasmocytic (n = 6), follicular (n = 1), and diffuse large B-cell (n = 1) lymphomas. Two other groups of lymphoproliferative disease were analyzed as controls. First, ten cases of nodal lymphomas (follicular and marginal zone B-cell lymphomas), and ten cases of reactive lymphoid hyperplasia were analyzed. A multiplex touchdown, enzyme time-release PCR designed to simultaneously detect C. psittaci, C. pneumoniae and C. trachomatis DNA sequences was performed. PCR analyses were performed in duplicate in an independent setting either inat the Curie Institut Curie in e, Paris, and in the National Cancer Institute, Aviano. Results: DNA of C. psittaci DNA was detected in the tumoral tissue of only one patient with follicular OAL. No DNA sequences of C. psittaci, C. pneumoniae and C. trachomatis DNA sequences were was detected in all any of the other OALs, or controls. Conclusions: The prevalence of C. psittaci infection in French pts with OAL was sensibly significantly lower than that reported in Italian series. Cross-controls between the two laboratories indicate that this finding is not due to different experimental conditions. Discrepancies may be explained by an heterogeneous epidemiological distribution of the bacterial infection. Large studies aimed to investigate geographical variations in the prevalence of this association are warranted. No significant financial relationships to disclose.


1983 ◽  
Vol 158 (6) ◽  
pp. 2165-2170 ◽  
Author(s):  
N Nogueira ◽  
G Kaplan ◽  
E Levy ◽  
E N Sarno ◽  
P Kushner ◽  
...  

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.


2017 ◽  
Vol 10 (2) ◽  
pp. 145-160 ◽  
Author(s):  
Mark S. Gresnigt ◽  
Katharina L. Becker ◽  
Floris Leenders ◽  
M. Fernanda Alonso ◽  
Xiaowen Wang ◽  
...  

Invasive aspergillosis mainly occurs in immunocompromised patients and is commonly caused by Aspergillus fumigatus, while A.nidulans is rarely the causative agent. However, in chronic granulomatous disease (CGD) patients, A. nidulans is a frequent cause of invasive aspergillosis and is associated with higher mortality. Immune recognition of A. nidulans was compared to A. fumigatus to offer an insight into why A. nidulans infections are prevalent in CGD. Live cell imaging with J774A.1 macrophage-like cells and LC3-GFP-mCherry bone marrow-derived macrophages (BMDMs) revealed that phagocytosis of A. nidulans was slower compared to A. fumigatus. This difference could be attributed to slower migration of J774A.1 cells and a lower percentage of migrating BMDMs. In addition, delayed phagosome acidification and LC3-associated phagocytosis was observed with A. nidulans. Cytokine and oxidative burst measurements in human peripheral blood mononuclear cells revealed a lower oxidative burst upon challenge with A. nidulans. In contrast, A. nidulans induced significantly higher concentrations of cytokines. Collectively, our data demonstrate that A. nidulans is phagocytosed and processed at a slower rate compared to A. fumigatus, resulting in reduced fungal killing and increased germination of conidia. This slower rate of A. nidulans clearance may be permissive for overgrowth within certain immune settings.


Parasitology ◽  
2018 ◽  
Vol 146 (3) ◽  
pp. 322-332 ◽  
Author(s):  
Gerusa B. Carvalho ◽  
Lourena E. Costa ◽  
Daniela P. Lage ◽  
Fernanda F. Ramos ◽  
Thaís T. O. Santos ◽  
...  

AbstractIn the current study, phage-exposed mimotopes as targets against tegumentary leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of TL patients and healthy subjects, besides the immune stimulation of peripheral blood mononuclear cells (PBMCs) collected from untreated and treated TL patients and healthy subjects. The clones were evaluated regarding their specific interferon-γ (IFN-γ) and interleukin-4 (IL-4) production in the in vitro cultures, and selectivity and specificity values were calculated, and those presenting the best results were selected for the in vivo experiments. Two clones, namely A4 and A8, were identified and used in immunization protocols from BALB/c mice to protect against Leishmania amazonensis infection. Results showed a polarized Th1 response generated after vaccination, being based on significantly higher levels of IFN-γ, IL-2, IL-12, tumour necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were associated with lower production of specific IL-4, IL-10 and immunoglobulin G1 (IgG1) antibodies. Vaccinated mice presented significant reductions in the parasite load in the infected tissue and distinct organs, when compared with controls. In conclusion, we presented a strategy to identify new mimotopes able to induce Th1 response in PBMCs from TL patients and healthy subjects, and that were successfully used to protect against L. amazonensis infection.


2020 ◽  
pp. 2002695 ◽  
Author(s):  
Elliott D. Crouser ◽  
Landon W. Locke ◽  
Mark W. Julian ◽  
Sabahattin Bicer ◽  
Wolfgang Sadee ◽  
...  

IntroductionSarcoidosis and tuberculosis are granulomatous pulmonary diseases characterised by heightened immune reactivity to Mycobacterium tuberculosis (M.tb.) antigens. We hypothesised that an unsupervised analysis comparing the molecular characteristics of granulomas formed in response to M.tb. antigens in patients with sarcoidosis or latent tuberculosis infection (LTBI) would provide novel insights into the pathogenesis of sarcoidosis.MethodsA genomic analysis identified differentially expressed (DE) genes in granuloma-like cell aggregates formed by sarcoidosis (n=12) or LTBI patients (n=5) in an established in vitro human granuloma model wherein peripheral blood mononuclear cells (PBMCs) were exposed to M.tb. antigens (beads coated with purified protein derivative, PPD) and cultured for 7 days. Pathway analysis of DE genes identified canonical pathways, most notably antigen processing and presentation via phagolysosomes, as a prominent pathway in sarcoidosis granuloma formation. The phagolysosomal pathway promoted mTORc1/STAT3 signal transduction. Thus, granuloma formation and related immune mediators were evaluated in the absence or presence of various pre-treatments known to prevent phagolysosome formation (chloroquine) or phagosome acidification (bafilomycin A1) or directly inhibit mTORc1 activation (rapamycin).ResultsIn keeping with genomic analyses indicating enhanced phagolysosomal activation and predicted mTORc1 signalling, it was determined that sarcoidosis granuloma formation and related inflammatory mediator release was dependent upon phagolysosome assembly and acidification and mTORc1/S6/STAT3 signal transduction.ConclusionsSarcoidosis granulomas exhibit enhanced and sustained intracellular antigen processing and presentation capacities, and related phagolysosome assembly and acidification are required to support mTORc1 signalling to promote sarcoidosis granuloma formation.


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