Interactions between immunity and chemotherapy in the treatment of the trypanosomiases and leishmaniases

Parasitology ◽  
1992 ◽  
Vol 105 (S1) ◽  
pp. S71-S78 ◽  
Author(s):  
B. J. Berger ◽  
A. H. Fairlamb
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Immune System ◽  
Leishmania Donovani ◽  
Immune Status ◽  
Cell Mediated Immune Response ◽  
Intact Immune System ◽  
Rapid Clearance ◽  
Increased Activity ◽  
Wall Components

SUMMARYThe immune status of a host infected withTrypanosomaspp. orLeishmaniaspp. can play an important role in successful chemotherapy. In animal models, treatment of African trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. An intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. Similarly, an efficient cell-mediated immune response is required for maximal efficacy of pentavalent antimonials in the treatment of leishmaniasis. However, the potential relationship between parasite-induced or acquired immunosuppression and effective chemotherapy has been poorly studied. Macrophages which have been activated by bacterial cell wall components or gamma-interferon are known to display increased activity againstLeishmania donovaniorTrypanosoma cruzi. In experimental and clinical visceral leishmaniasis, use of macrophage activators together with pentavalent antimonials has lowered the dose of antimony required to cure the infection.

scholarly journals Leishmania donovani Secretory Mevalonate Kinase Regulates Host Immune Response and Facilitates Phagocytosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Tanvir Bamra ◽  
Taj Shafi ◽  
Sushmita Das ◽  
Manjay Kumar ◽  
Manas Ranjan Dikhit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Leishmania Donovani ◽  
Indian Subcontinent ◽  
Parasite Burden ◽  
Host Immune Response ◽  
Host Cells ◽  
Interleukin 4 ◽  
Host Immune System ◽  
Mevalonate Kinase

Summary StatementLeishmania secretes over 151 proteins during in vitro cultivation. Cellular functions of one such novel protein: mevalonate kinase is discussed here; signifying its importance in Leishmania infection.Visceral Leishmaniasis is a persistent infection, caused by Leishmania donovani in Indian subcontinent. This persistence is partly due to phagocytosis and evasion of host immune response. The underlying mechanism involves secretory proteins of Leishmania parasite; however, related studies are meagre. We have identified a novel secretory Leishmania donovani glycoprotein, Mevalonate kinase (MVK), and shown its importance in parasite internalization and immuno-modulation. In our studies, MVK was found to be secreted maximum after 1 h temperature stress at 37°C. Its secretion was increased by 6.5-fold in phagolysosome-like condition (pH ~5.5, 37°C) than at pH ~7.4 and 25°C. Treatment with MVK modulated host immune system by inducing interleukin-10 and interleukin-4 secretion, suppressing host’s ability to kill the parasite. Peripheral blood mononuclear cell (PBMC)-derived macrophages infected with mevalonate kinase-overexpressing parasites showed an increase in intracellular parasite burden in comparison to infection with vector control parasites. Mechanism behind the increase in phagocytosis and immunosuppression was found to be phosphorylation of mitogen-activated protein (MAP) kinase pathway protein, Extracellular signal-regulated kinases-1/2, and actin scaffold protein, cortactin. Thus, we conclude that Leishmania donovani Mevalonate kinase aids in parasite engulfment and subvert the immune system by interfering with signal transduction pathways in host cells, which causes suppression of the protective response and facilitates their persistence in the host. Our work elucidates the involvement of Leishmania in the process of phagocytosis which is thought to be dependent largely on macrophages and contributes towards better understanding of host pathogen interactions.

scholarly journals Elotuzumab Enhances the Th2-Mediated Immune Response of Dendritic Cell Induced By Immunomodulatory Drugs (IMiDs)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4342-4342
Author(s):  
Yoshiko Azuma ◽  
Tomoki Ito ◽  
Muneo Inaba ◽  
Kai Imai ◽  
Masaaki Hotta ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Dendritic Cell ◽  
Humoral Immunity ◽  
Immune Status ◽  
Fold Increase ◽  
Immune Dysfunction ◽  
Th2 Response ◽  
Humoral Immune ◽  
Before And After

Background: Elotuzumab, a humanized IgG1 monoclonal antibody targeting SLAMF7, is useful for the treatment of Relapsed or Refractory multiple myeloma (RRMM) in combination with Lenalidomide (LEN). However, cellular and molecular mechanisms underlying the immunomodulatory effects of elotuzumab still remain largely unclear. We have previously reported that LEN displays immunopotentiating activity that enhances Th2-mediated response at dendritic cell (DC) phase as upstream immune cascade associated with humoral immunity. DCs are pivotal cells in the sense of orchestrating both cell-mediated (linking with Th1) and humoral (linking with Th2) immunity as masters of the immune system. Series of analyses have clarified myeloid DCs (mDCs) play an important role in allergic immune response by the induction of Th2 response. Here, we focused on the effects of elotuzumab in combination with LEN on the function of human mDCs. Methods: Purified blood human CD11+ mDCs from healthy adult volunteers using cell sorting were cultured and analyzed by flow cytometry and ELISA. Serum were obtained from 16 MM patients with before and after elotuzumab therapy. This study was approved by the Institutional Review Board of Kansai Medical University. Results: We found that surface expression of SLAMF7 on mDCs was upregulated in response to Th2-inducing cytokine, thymic stromal lymphopoietin (TSLP) and the expression level was higher in response to TSLP than in response to toll-like receptor ligand R848. Elotuzumab at clinical in vivo plasma concentration of 30 to 300 µg/ml did not affect mDC survival and their CD86 and OX40-ligand expression when stimulated with 0.3 µM LEN and/or TSLP for 24 h. LEN enhanced TSLP-mediated Th2-recruiting chemokine CCL17/TARC from mDCs which functions as chemoattractant for memory Th2 cells and contribute to allergy and humoral immune responses, and elotuzumab significantly enhanced the LEN-mediated production of CCL17/TARC (TSLP+LEN as control vs. TSLP+LEN+100 µg/ml elotuzumab; 1.23 fold increase: p=0.003, and control vs. TSLP+LEN+300 µg/ml elotuzumab; 1.38 fold increase: p=0.038). This finding suggest elotuzumab enhances Th2-mediated immune profile at upstream phase of humoral immunity. In addition, serum CCL17 levels were analyzed in RRMM patients before and after 3 cycle elotuzumab administration (n=16). We found, serum CCL17 levels after elotuzumab administration were significantly higher compared with those before elotuzumab treatment (after; 1512 ± 459 pg/ml vs. before; 402.2 ± 87.4 pg/ml: p = 0.013). Conclusion: MM involves an element of humoral immune dysfunction. Immune status is important for the prognosis of MM, and clinical outcome can be improved by the recovery of immune status. In this context, our data showing the enhancement of Th2-mediated response by elotuzumab provide a plausible explanation for the observed clinical benefit of this antibody-drug in MM. This function of elotuzumab seems to be relevant to the treatment of MM patients under humoral immune dysfunction. Based on our data in focusing on DCs in the immune system, elotuzumab and IMiDs could function as immunostimulators of humoral immunity via mDCs, and this finding elucidated an additional cellular target of elotuzumab. Disclosures Ito: Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding.

scholarly journals Fungal Cell Wall Components Modulate our Immune System

2021 ◽  
pp. 100067
Author(s):  
Benoit Briard ◽  
Thierry Fontaine ◽  
Thirumala-Devi Kanneganti ◽  
Neil A.R. Gow ◽  
Nicolas Papon
Keyword(s):  
Cell Wall ◽  
Immune System ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Cell Wall Components ◽  
Wall Components

scholarly journals Nonprotein Structures from Mycobacteria: Emerging Actors for Tuberculosis Control

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Luz M. Lopez-Marin
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Current Knowledge ◽  
Protein Structures ◽  
New Developments ◽  
Immune Modulators ◽  
Human Immune Response ◽  
Human Immune ◽  
Mycobacterial Cell Wall ◽  
Wall Components

Immune response toMycobacterium tuberculosis, the causal agent of tuberculosis, is critical for protection. For many decades, consistent to classical biochemistry, most studies regarding immunity to the tubercle bacilli focused mainly on protein structures. But the atypical, highly impermeable and waxy coat of mycobacteria captured the interest of structural biologists very early, allowing the description of amazing molecules, such as previously unknown carbohydrates or fatty acids of astonishing lengths. From their discovery, cell wall components were identified as important structural pillars, but also as molecular motifs able to alter the human immune response. Recently, as new developments have emerged, classical conceptions of mycobacterial immune modulators have been giving place to unexpected discoveries that, at the turn of the last century, completely changed our perception of immunityvis-à-visfat compounds. In this paper, current knowledge about chemical and ultrastructural features of mycobacterial cell-wall is overviewed, with an emphasis on the relationships between cell-wall nonpeptide molecules and immune response. Remarks regarding the potential of these molecules for the development of new tools against tuberculosis are finally discussed.

scholarly journals METABOLIC DETERMINANTS OF IMMUNE REACTIVITY

2017 ◽  
Vol 19 (3) ◽  
pp. 56-63
Author(s):  
Dmitry A Vologzhanin ◽  
Yuriy Sh Khalimov
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Status ◽  
Severe Trauma ◽  
The State ◽  
Immune Reactivity ◽  
The Moment

As a result of the study of the dynamics of nutritional and immune status in patients with severe trauma in the first 30 days of the posttraumatic period, the interrelations between the parameters of metabolism and the immune system were revealed and the predominant influence of a number of nutrients on the state of the various type of immune response was revealed. Data were obtained indicating the change in the need for immunonutrients at different times from the moment of injury. Prospective approaches to nutritional immunocorrection in patients with trauma, consisting in the differential use of separate nutrients at different period after trauma, have been identified (9 figs, bibliography: 9 refs).

scholarly journals Features of immune response in chronic exposure to industrial aerosols

2019 ◽  
Vol 95 (11) ◽  
pp. 1058-1061
Author(s):  
Elena N. Kryuchkova ◽  
L. M. Saarkoppel ◽  
I. V. Yatsyna
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Humoral Immunity ◽  
Cellular Immunity ◽  
Chronic Exposure ◽  
Immune Status ◽  
Cytokine Profile ◽  
Dust Aerosols

There are considered features of disorders of the immune response in chronic exposure to dust aerosols. The detected changes of indices of the immune status of employees of the dust dangerous occupations and patients with chronic dust pathology of the lungs were unidirectional in the character, which is probably caused by manifestations of nonspecific response of the immune system to the dust factor. The deterioration of cellular immunity, humoral immunity and cytokine profile predisposes to the occurrence of immunopathologic states, contributing to the development of caused by both worksite and occupation pathology.

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