Trypanosoma cruzi: Do different sylvatic strains trigger distinct immune responses?

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

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Cellular Immune Responses of Chagasic Patients to Antigens Derived from Different Trypanosoma Cruzi Strains and Clones

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.1986.35.505 ◽

1986 ◽

Vol 35 (3) ◽

pp. 505-511 ◽

Cited By ~ 26

Author(s):

Maria José F. Morato ◽

Giovanni Gazzinelli ◽

Joaquim R. Cançado ◽

Rosa Maria B. Nunes ◽

Egler Chiari ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Cellular Immune Responses ◽

Cellular Immune

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Intranasal Vaccinations with the trans-Sialidase Antigen plus CpG Adjuvant Induce Mucosal Immunity Protective against Conjunctival Trypanosoma cruzi Challenges

Infection and Immunity ◽

10.1128/iai.00278-09 ◽

2010 ◽

Vol 78 (3) ◽

pp. 1333-1338 ◽

Cited By ~ 18

Author(s):

O. K. Giddings ◽

C. S. Eickhoff ◽

N. L. Sullivan ◽

D. F. Hoft

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Body Fluid ◽

Direct Evidence ◽

Protozoan Parasite ◽

Secretory Iga ◽

Parasite Invasion ◽

Mucosal Surfaces ◽

Parasite Replication ◽

Intracellular Protozoan Parasite

ABSTRACT Trypanosoma cruzi is an intracellular protozoan parasite capable of infecting through mucosal surfaces. Our laboratory has previously elucidated the anatomical routes of infection after both conjunctival and gastric challenge in mice. We have shown that chronically infected mice develop strong immune responses capable of protecting against subsequent rechallenge with virulent parasites through gastric, conjunctival, and systemic routes of infection. We have also shown that intranasal immunizations with the unique T. cruzi trans-sialidase (TS) antigen protect against gastric and systemic T. cruzi challenge. In the current work we have investigated the ability of purified TS adjuvanted with CpG-containing oligonucleotides to induce immunity against conjunctival T. cruzi challenge. We confirm that intranasal vaccinations with TS plus CpG induce TS-specific T-cell and secretory IgA responses. TS-specific secretory IgA was detectable in the tears of vaccinated mice, the initial body fluid that contacts the parasite during infectious conjunctival exposures. We further show that intranasal vaccinations with TS plus CpG protect against conjunctival T. cruzi challenge, limiting local parasite replication at the site of mucosal invasion and systemic parasite dissemination. We also provide the first direct evidence that mucosal antibodies induced by intranasal TS vaccination can inhibit parasite invasion.

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Is It Possible to Intervene in the Capacity of Trypanosoma cruzi to Elicit and Evade the Complement System?

Frontiers in Immunology ◽

10.3389/fimmu.2021.789145 ◽

2021 ◽

Vol 12 ◽

Author(s):

Galia Ramírez-Toloza ◽

Lorena Aguilar-Guzmán ◽

Carolina Valck ◽

Smrithi S. Menon ◽

Viviana P. Ferreira ◽

...

Keyword(s):

Latin America ◽

Trypanosoma Cruzi ◽

Immune Responses ◽

Chagas Disease ◽

Complement System ◽

Significant Inhibition ◽

Transplacental Transmission ◽

Global Expansion ◽

The Complement System ◽

Evasive Strategy

Chagas’ disease is a zoonotic parasitic ailment now affecting more than 6 million people, mainly in Latin America. Its agent, the protozoan Trypanosoma cruzi, is primarily transmitted by endemic hematophagous triatomine insects. Transplacental transmission is also important and a main source for the emerging global expansion of this disease. In the host, the parasite undergoes intra (amastigotes) and extracellular infective (trypomastigotes) stages, both eliciting complex immune responses that, in about 70% of the cases, culminate in permanent immunity, concomitant with the asymptomatic presence of the parasite. The remaining 30% of those infected individuals will develop a syndrome, with variable pathological effects on the circulatory, nervous, and digestive systems. Herein, we review an important number of T. cruzi molecules, mainly located on its surface, that have been characterized as immunogenic and protective in various experimental setups. We also discuss a variety of parasite strategies to evade the complement system - mediated immune responses. Within this context, we also discuss the capacity of the T. cruzi infective trypomastigote to translocate the ER-resident chaperone calreticulin to its surface as a key evasive strategy. Herein, it is described that T. cruzi calreticulin inhibits the initial stages of activation of the host complement system, with obvious benefits for the parasite. Finally, we speculate on the possibility to experimentally intervene in the interaction of calreticulin and other T. cruzi molecules that interact with the complement system; thus resulting in significant inhibition of T. cruzi infectivity.

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The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.758273 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jorge Nihei ◽

Fabiola Cardillo ◽

Jose Mengel

Keyword(s):

Immune Response ◽

T Cells ◽

Regulatory T Cells ◽

Trypanosoma Cruzi ◽

Immune Responses ◽

Chagas Disease ◽

Acute Phase ◽

Acute Infection ◽

Dependent Manner ◽

Tissue Specific

Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection progresses to a chronic stage. The parasite infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart muscle, among many others. It is evident now that tissue-specific immune responses may develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity and to ensure tissue-specific tolerance are operating during the infection. Studying those immunoregulatory mechanisms is fundamental to improve host protection or control inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection is not established. IL-2 production by T cells is strongly down-modulated early in the disease by unknown mechanisms and remains low during the chronic phase of the disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity development. Also, the expansion and maintenance of regulatory T cells require IL-2. Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune responses, probably in a dose-dependent manner. This study blocked IL-2 during the acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that parasitemia and mortality rate was lower in animals treated with anti-IL-2. The percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T cells increased during the acute infection. T cells producing IFN-γ, TNF-α and IL-10 also augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17 produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation through the expansion/maintenance of regulatory T cells and regulating IL-17 production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes in acute and chronic phases of Chagas’ disease.

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Salivary and Intestinal Transcriptomes Reveal Differential Gene Expression in Starving, Fed and Trypanosoma cruzi-Infected Rhodnius neglectus

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.773357 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tamires Marielem Carvalho-Costa ◽

Rafael Destro Rosa Tiveron ◽

Maria Tays Mendes ◽

Cecília Gomes Barbosa ◽

Jessica Coraiola Nevoa ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Blood Feeding ◽

Future Research ◽

Transcriptional Expression ◽

Potential Vector ◽

Expression Of Genes ◽

Short Period ◽

Differential Gene ◽

Antigen 5

Rhodnius neglectus is a potential vector of Trypanosoma cruzi (Tc), the causative agent of Chagas disease. The salivary glands (SGs) and intestine (INT) are actively required during blood feeding. The saliva from SGs is injected into the vertebrate host, modulating immune responses and favoring feeding for INT digestion. Tc infection significantly alters the physiology of these tissues; however, studies that assess this are still scarce. This study aimed to gain a better understanding of the global transcriptional expression of genes in SGs and INT during fasting (FA), fed (FE), and fed in the presence of Tc (FE + Tc) conditions. In FA, the expression of transcripts related to homeostasis maintenance proteins during periods of stress was predominant. Therefore, the transcript levels of Tret1-like and Hsp70Ba proteins were increased. Blood appeared to be responsible for alterations found in the FE group, as most of the expressed transcripts, such as proteases and cathepsin D, were related to digestion. In FE + Tc group, there was a decreased expression of blood processing genes for insect metabolism (e.g., Antigen-5 precursor, Pr13a, and Obp), detoxification (Sult1) in INT and acid phosphatases in SG. We also found decreased transcriptional expression of lipocalins and nitrophorins in SG and two new proteins, pacifastin and diptericin, in INT. Several transcripts of unknown proteins with investigative potential were found in both tissues. Our results also show that the presence of Tc can change the expression in both tissues for a long or short period of time. While SG homeostasis seems to be re-established on day 9, changes in INT are still evident. The findings of this study may be used for future research on parasite-vector interactions and contribute to the understanding of food physiology and post-meal/infection in triatomines.

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Strain-specific genome evolution in Trypanosoma cruzi, the agent of Chagas disease

PLoS Pathogens ◽

10.1371/journal.ppat.1009254 ◽

2021 ◽

Vol 17 (1) ◽

pp. e1009254

Author(s):

Wei Wang ◽

Duo Peng ◽

Rodrigo P. Baptista ◽

Yiran Li ◽

Jessica C. Kissinger ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Gene Amplification ◽

Gene Diversity ◽

Gene Families ◽

Copy Number Variations ◽

Host Immune Responses ◽

Large Gene ◽

Genes Encoding ◽

Long Read

The protozoan Trypanosoma cruzi almost invariably establishes life-long infections in humans and other mammals, despite the development of potent host immune responses that constrain parasite numbers. The consistent, decades-long persistence of T. cruzi in human hosts arises at least in part from the remarkable level of genetic diversity in multiple families of genes encoding the primary target antigens of anti-parasite immune responses. However, the highly repetitive nature of the genome–largely a result of these same extensive families of genes–have prevented a full understanding of the extent of gene diversity and its maintenance in T. cruzi. In this study, we have combined long-read sequencing and proximity ligation mapping to generate very high-quality assemblies of two T. cruzi strains representing the apparent ancestral lineages of the species. These assemblies reveal not only the full repertoire of the members of large gene families in the two strains, demonstrating extreme diversity within and between isolates, but also provide evidence of the processes that generate and maintain that diversity, including extensive gene amplification, dispersion of copies throughout the genome and diversification via recombination and in situ mutations. Gene amplification events also yield significant copy number variations in a substantial number of genes presumably not required for or involved in immune evasion, thus forming a second level of strain-dependent variation in this species. The extreme genome flexibility evident in T. cruzi also appears to create unique challenges with respect to preserving core genome functions and gene expression that sets this species apart from related kinetoplastids.

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