scholarly journals Rosettes integrity protects Plasmodium vivax of being phagocytized

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Letusa Albrecht ◽  
Stefanie C. P. Lopes ◽  
Ana Beatriz Iung Enembreck da Silva ◽  
Vanessa Barbosa ◽  
Rodrigo P. Almeida ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Vivax ◽  
Immune Evasion ◽  
Ex Vivo ◽  
Immunoglobulin M ◽  
Phagocytosis Assay ◽  
Evasion Strategy ◽  
Peripheral Leukocytes ◽  
Total Immunoglobulin

Abstract Plasmodium vivax is the most prevalent cause of malaria outside of Africa. P. vivax biology and pathogenesis are still poorly understood. The role of one highly occurring phenotype in particular where infected reticulocytes cytoadhere to noninfected normocytes, forming rosettes, remains unknown. Here, using a range of ex vivo approaches, we showed that P. vivax rosetting rates were enhanced by plasma of infected patients and that total immunoglobulin M levels correlated with rosetting frequency. Moreover, rosetting rates were also correlated with parasitemia, IL-6 and IL-10 levels in infected patients. Transcriptomic analysis of peripheral leukocytes from P. vivax-infected patients with low or moderated rosetting rates identified differentially expressed genes related to human host phagocytosis pathway. In addition, phagocytosis assay showed that rosetting parasites were less phagocyted. Collectively, these results showed that rosette formation plays a role in host immune response by hampering leukocyte phagocytosis. Thus, these findings suggest that rosetting could be an effective P. vivax immune evasion strategy.

Immunotherapy: New insights in breast cancer treatment

2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Treatment ◽  
Immune Evasion ◽  
Breast Tumor ◽  
Parp Inhibitor ◽  
Breast Cancer Treatment ◽  
New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

scholarly journals A simple, ex vivo phagocytosis assay of Plasmodium vivax merozoites by flow cytometry

2019 ◽  
Vol 114 ◽  
Author(s):  
Elizangela Farias ◽  
Fhabiane Bezerra ◽  
Djane Clarys Baia-da-Silva ◽  
Yury Oliveira Chaves ◽  
Tatiana Bacry Cardoza ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Plasmodium Vivax ◽  
Ex Vivo ◽  
Phagocytosis Assay

CD209 (DC-SIGN) – role in the work of the innate immunity and pathogen penetration

2020 ◽  
Vol 1 (9) ◽  
pp. 64-71
Author(s):  
E. A. Klimov ◽  
◽  
E. K. Novitskaya ◽  
S. N. Koval’chuk ◽  
◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Adhesion Molecule ◽  
Immune Evasion ◽  
Intercellular Adhesion Molecule ◽  
Lectin Receptor

Intercellular adhesion molecule CD209 (DC-SIGN) is a membrane C-type lectin receptor expressed on the surface of dendritic cells and macrophages. CD209 plays an important role in innate immunity. Many studies have shown the possibility of interaction of the CD209 molecule with a number of dangerous pathogens of humans and animals. This review summarizes information on the structure of the CD209 gene and its product, describes the role of the CD209 protein in the immune response, in the migration of dendritic cells from the blood to the tissue, and their interaction with neutrophils. The currently known signaling pathway of activation through the CD209 inflammatory response is presented. The role of CD209 as an endocytic antigen receptor and the participation of the protein in immune evasion of pathogens are discussed. The mechanisms known to date for the development of infections caused by pathogens of various nature in animals are described.

scholarly journals Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Anne C. G. Almeida ◽  
Maria C. B. Puça ◽  
Erick F. G. Figueiredo ◽  
Laila R. Barbosa ◽  
Yanka E. A. R. Salazar ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Ex Vivo ◽  
Plasma Concentrations ◽  
Similar Efficacy ◽  
Early Recurrence ◽  
Control Group ◽  
Recurrence Rates ◽  
Mutant Genotype ◽  
Content Type

ABSTRACT Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism.

scholarly journals Role of Bordetella bronchisepticaFimbriae in Tracheal Colonization and Development of a Humoral Immune Response

2000 ◽  
Vol 68 (4) ◽  
pp. 2024-2033 ◽  
Author(s):  
Seema Mattoo ◽  
Jeff F. Miller ◽  
Peggy A. Cotter
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Limit Of Detection ◽  
Immunoglobulin M ◽  
Tissue Culture Cell ◽  
Wild Type ◽  
Humoral Immune ◽  
Tract Infections

ABSTRACT Fimbriae are filamentous, cell surface structures which have been proposed to mediate attachment of Bordetella species to respiratory epithelium. Bordetella bronchiseptica has four known fimbrial genes: fim2, fim3,fimX, and fimA. While these genes are unlinked on the chromosome, their protein products are assembled and secreted by a single apparatus encoded by the fimBCD locus. ThefimBCD locus is embedded within the fha operon, whose genes encode another putative adhesin, filamentous hemagglutinin (FHA). We have constructed a Fim− B. bronchiseptica strain, RB63, by introducing an in-frame deletion extending from fimB through fimD. Western blot analysis showed that RB63 is unable to synthesize fimbriae but is unaffected for FHA expression. Using this mutant, we assessed the role of fimbriae in pathogenesis in vitro and in vivo in natural animal hosts. Although RB63 was not significantly defective in its ability to adhere to various tissue culture cell lines, including human laryngeal HEp-2 cells, it was considerably altered in its ability to cause respiratory tract infections in rats. The number of ΔfimBCD bacteria recovered from the rat trachea at 10 days postinoculation was significantly decreased compared to that of wild-type B. bronchiseptica and was below the limit of detection at 30 and 60 days postinoculation. The number of bacteria recovered from the nasal cavity and larynx was not significantly different between RB63 and the wild-type strain at any time point. The ability of fimbriae to mediate initial attachment to tracheal tissue was tested in an intratracheal inoculation assay. Significantly fewer RB63 than wild-type bacteria were recovered from the tracheas at 24 h after intratracheal inoculation. These results demonstrate that fimbriae are involved in enhancing the ability of B. bronchiseptica to establish tracheal colonization and are essential for persistent colonization at this site. Interestingly, anti-Bordetella serum immunoglobulin M (IgM) levels were significantly lower in animals infected with RB63 than in animals infected with wild-type B. bronchiseptica at 10 days postinoculation. Even at 30 days postinoculation, RB63-infected animals had lower serum anti-Bordetella antibody titers in general. This disparity in antibody profiles suggests that fimbriae are also important for the induction of a humoral immune response.

scholarly journals B-Cell-Deficient Mice Show an Exacerbated Inflammatory Response in a Model of Chlamydophila abortus Infection

2002 ◽  
Vol 70 (12) ◽  
pp. 6911-6918 ◽  
Author(s):  
Antonio J. Buendía ◽  
Laura Del Río ◽  
Nieves Ortega ◽  
Joaquín Sánchez ◽  
María C. Gallego ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Immunoglobulin M ◽  
Chlamydia Psittaci ◽  
Chlamydophila Abortus ◽  
Serotype 1

ABSTRACT The resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection is dependent on gamma interferon and CD8+ T cells, and classically, B cells have been considered to play a minimal role in host defense. The role of B cells in the immune response was studied by using a model of infection in mice with genetically modified immunoglobulin M transmembrane domains (μMT). In the absence of B cells, infection with C. abortus leads to an acute severe fatal disease that involves a disseminated intravascular coagulation syndrome. μMT mice displayed an increased level of proinflammatory cytokines in serum, and an increased number of neutrophils was observed in the lesions. The possible deleterious role of neutrophils in the pathogenesis of disease in μMT mice was determined by depletion of the neutrophils with the monoclonal antibody RB6-8C5. This led to an enhancement of the bacterial burden and early mortality in both μMT and wild-type mice, while necrotic lesions remained. Analysis of the presence of immunoregulatory cytokines showed significantly lower levels of transforming growth factor β in the sera of μMT mice. However, mice lacking mature B cells were able to establish a specific immune response that protected them from a secondary challenge. Taken together, these data suggest an immunomodulatory role for B cells in the early events of C. abortus primary infection that can protect mice against an exaggerated inflammatory response.

Attenuation of immune-mediated glomerulonephritis with an anti-CD11b monoclonal antibody

1993 ◽  
Vol 264 (4) ◽  
pp. F715-F721 ◽  
Author(s):  
X. Wu ◽  
J. Pippin ◽  
J. B. Lefkowith
Keyword(s):  
Monoclonal Antibody ◽  
Ex Vivo ◽  
Neutrophil Migration ◽  
Surface Receptors ◽  
Eicosanoid Production ◽  
Immune Mediated ◽  
Disease Induction ◽  
Peripheral Leukocytes

Nephrotoxic nephritis (NTN), a model of autoimmune glomerulonephritis, is characterized by glomerular inflammation, which results in both proteinuria and an increase in eicosanoid production. In light of the ability of CD18 integrins to participate in leukocyte adherence (and thereby migration), we examined the role of the integrin CD11b/CD18 in NTN using OX42, a monoclonal antibody directed against rat CD11b. Administration of OX42 30 min before induction of NTN decreased proteinuria (by 50%) but did not affect the number of leukocytes found in the glomerulus or the accompanying increase in glomerular eicosanoid production. Administration of OX42 16 h before disease induction led to a more substantial decrease in proteinuria (80%) and, in contrast to 30 min pretreatment, decreased the number of neutrophils found in the glomerulus and the accompanying increase in glomerular eicosanoid production (both by 50%). OX42 pretreatment had no effect on the number of macrophages found in glomeruli. Circulating leukocytes from animals treated with OX42 in vivo showed saturating surface levels of antibody by fluorescence-activated cell sorting (FACS) analysis and normal upregulation of CD11b by pharmacological activation. Sixteen hours after in vivo injection of OX42, 50% more peripheral leukocytes were labeled relative to control leukocytes labeled with OX42 ex vivo. Glomerular leukocytes in NTN exhibited upregulated expression of CD11b relative to peripheral leukocytes. These data show that CD11b/CD18 may participate in the acute expression of glomerular damage in NTN in a fashion not wholly dependent on blocking neutrophil migration into glomeruli. Blockade of surface receptors (as opposed to inhibition of upregulation) is sufficient to obtain this effect.

scholarly journals Mechanisms of immune evasion in bladder cancer

2019 ◽  
Vol 69 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Paul L. Crispen ◽  
Sergei Kusmartsev
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
Tumor Microenvironment ◽  
Immune Evasion ◽  
Cancer Biology ◽  
Checkpoint Inhibitors ◽  
New Agents ◽  
Multiple Trials ◽  
Checkpoint Inhibitor Therapy

AbstractWith the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host’s immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.

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