Anatomical Route of Invasion and Protective Mucosal Immunity in Trypanosoma cruzi Conjunctival Infection

ABSTRACT Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection after conjunctival exposure. The anatomical route of T. cruzi invasion and spread after conjunctival parasite contamination remains poorly characterized. In the present work we have identified the sites of initial invasion and replication after contaminative conjunctival challenges with T. cruzi metacyclic trypomastigotes using a combination of immunohistochemical and real-time PCR confirmatory techniques in 56 mice between 3 and 14 days after challenge. Our results demonstrate that the predominant route of infection involves drainage of parasites through the nasolacrimal duct into the nasal cavity. Initial parasite invasion occurs within the ductal and respiratory epithelia. After successive waves of intracellular replication and cell-to-cell spread, parasites drain via local lymphatic channels to lymph nodes and then disseminate through the blood to distant tissues. This model of conjunctival challenge was used to identify immune responses associated with protection against mucosal infection. Preceding mucosal infection induces mucosal immunity, resulting in at least 50-fold reductions in recoverable tissue parasite DNA in immune mice compared to controls 10 days after conjunctival challenge (P < 0.05). Antigen-specific gamma interferon production by T cells was increased at least 100-fold in cells harvested from immune mice (P < 0.05). Mucosal secretions containing T. cruzi-specific secretory immunoglobulin A harvested from immune mice were shown to protect against mucosal parasite infection (P < 0.05), demonstrating that mucosal antibodies can play a role in T. cruzi immunity. This model provides an important tool for detailed studies of mucosal immunity necessary for the development of mucosal vaccines.

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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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Galectins in Chagas Disease: A Missing Link Between Trypanosoma cruzi Infection, Inflammation, and Tissue Damage

Frontiers in Microbiology ◽

10.3389/fmicb.2021.794765 ◽

2022 ◽

Vol 12 ◽

Author(s):

Carolina V. Poncini ◽

Alejandro F. Benatar ◽

Karina A. Gomez ◽

Gabriel A. Rabinovich

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Tissue Damage ◽

Protozoan Parasite ◽

Multiple Roles ◽

Health Concern ◽

Global Public Health ◽

Parasite Invasion ◽

Socioeconomic Consequences ◽

Cruzi Infection

Trypanosoma cruzi, the protozoan parasite causative agent of Chagas disease, affects about seven million people worldwide, representing a major global public health concern with relevant socioeconomic consequences, particularly in developing countries. In this review, we discuss the multiple roles of galectins, a family of β-galactoside-binding proteins, in modulating both T. cruzi infection and immunoregulation. Specifically, we focus on galectin-driven circuits that link parasite invasion and inflammation and reprogram innate and adaptive immune responses. Understanding the dynamics of galectins and their β-galactoside-specific ligands during the pathogenesis of T. cruzi infection and elucidating their roles in immunoregulation, inflammation, and tissue damage offer new rational opportunities for treating this devastating neglected disease.

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Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

Frontiers in Immunology ◽

10.3389/fimmu.2013.00216 ◽

2013 ◽

Vol 4 ◽

Cited By ~ 11

Author(s):

Juliana de Meis ◽

Juliana Barreto de Albuquerque ◽

Danielle Silva dos Santos ◽

Désio Aurélio Farias-de-Oliveira ◽

Luiz Ricardo Berbert ◽

...

Keyword(s):

Immune Response ◽

Trypanosoma Cruzi ◽

Acute Infection ◽

Mucosal Infection

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Antigen-Specific Immunoglobulin A Antibodies Secreted from Circulating B Cells Are an Effective Marker for Recent Local Immune Responses in Patients with Cholera: Comparison to Antibody-Secreting Cell Responses and Other Immunological Markers

Infection and Immunity ◽

10.1128/iai.71.8.4808-4814.2003 ◽

2003 ◽

Vol 71 (8) ◽

pp. 4808-4814 ◽

Cited By ~ 64

Author(s):

Firdausi Qadri ◽

Edward T. Ryan ◽

A. S. G. Faruque ◽

Firoz Ahmed ◽

Ashraful Islam Khan ◽

...

Keyword(s):

Immune Responses ◽

Immunoglobulin A ◽

Peripheral Circulation ◽

Secreting Cell ◽

Antibody Secreting Cell ◽

Immunological Responses ◽

B Subunit ◽

Mucosal Infection ◽

Circulating Lymphocytes

ABSTRACT Gut-derived lymphocytes transiently migrate through the peripheral circulation before homing back to mucosal sites and can be detected using an ELISPOT-based antibody secreting cell (ASC) assay. Alternatively, transiently circulating lymphocytes may be cultured in vitro, and culture supernatants may be assayed for antigen-specific responses (antibody in lymphocyte supernatant [ALS] assay). The ALS assay has not been validated extensively in natural mucosal infection, nor has the ALS response been compared to the ASC assay and other cholera-specific immunological responses. Accordingly, we examined immune responses in 30 adult patients with acute cholera in Bangladesh, compared with 10 healthy controls, measuring ALS-immunoglobulin A (IgA), ASC-IgA, and serum and fecal IgA responses to two potent Vibrio cholerae immunogens, the nontoxic B subunit of cholera toxin (CtxB) and lipopolysaccharide (LPS) and a weaker V. cholerae immunogen, the mannose-sensitive hemagglutinin (MSHA). We found significant increases of anti-CtxB, anti-LPS, and anti-MSHA IgA in supernatants of lymphocytes cultured 7 days after onset of cholera using the ALS assay. We found that ALS and ASC responses correlated extremely well; both had comparable sensitivities as the vibriocidal responses, and both procedures were more sensitive than fecal IgA measurements. An advantage of the ALS assay for studying mucosal immune responses is the ability to freeze antibodies in supernatants for subsequent evaluation; like the ASC assay, the ALS assay can distinguish recent from remote mucosal infection, a distinction that may be difficult to make in endemic settings using other procedures.

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Machine Learning Techniques for the Automated Classification of Adhesin-Like Proteins in the Human Protozoan Parasite Trypanosoma cruzi

IEEE/ACM Transactions on Computational Biology and Bioinformatics ◽

10.1109/tcbb.2008.125 ◽

2009 ◽

Vol 6 (4) ◽

pp. 695-702 ◽

Cited By ~ 3

Author(s):

A.M. Gonzalez ◽

F.J. Azuaje ◽

J.L. Ramirez ◽

J.F. da Silveira ◽

J.R. Dorronsoro

Keyword(s):

Machine Learning ◽

Trypanosoma Cruzi ◽

Protozoan Parasite ◽

Machine Learning Techniques ◽

Automated Classification ◽

Learning Techniques

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Mucosal vaccines to prevent porcine reproductive and respiratory syndrome: a new perspective

Animal Health Research Reviews ◽

10.1017/s1466252312000023 ◽

2012 ◽

Vol 13 (1) ◽

pp. 21-37 ◽

Cited By ~ 13

Author(s):

Gourapura J. Renukaradhya ◽

Varun Dwivedi ◽

Cordelia Manickam ◽

Basavaraj Binjawadagi ◽

David Benfield

Keyword(s):

Mucosal Immunity ◽

Protective Immunity ◽

Mucosal Immune Response ◽

Respiratory Pathogens ◽

Swine Industry ◽

Prrs Virus ◽

Mucosal Vaccines ◽

Direct Delivery ◽

New Perspective ◽

Swine Herds

AbstractPorcine reproductive and respiratory syndrome (PRRS) is an economically important infectious disease of swine. Constant emergence of variant strains of PRRS virus (PPRSV) and virus-mediated immune evasion followed by viral persistence result in increased incidence and recurrence of PRRS in swine herds. Current live and killed PRRSV vaccines administered by a parenteral route are ineffective in inducing complete protection. Thus, new approaches in design and delivery of PRRSV vaccines are needed to reduce the disease burden of the swine industry. Induction of an effective mucosal immunity to several respiratory pathogens by direct delivery of a vaccine to mucosal sites has proven to be effective in a mouse model. However, there are challenges in eliciting mucosal immunity to PRRS due to our limited understanding of safe and potent mucosal adjuvants, which could potentiate the mucosal immune response to PRRSV. The purpose of this review is to discuss methods for induction of protective mucosal immune responses in the respiratory tract of pigs. The manuscript also discusses how PRRSV modulates innate, adaptive and immunoregulatory responses at both mucosal and systemic sites of infected and/or vaccinated pigs. This information may help in the design of innovative mucosal vaccines to elicit superior cross-protective immunity against divergent field strains of PRRSV.

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Temperature, Mitochondria, and Reye's Syndrome

PEDIATRICS ◽

10.1542/peds.71.6.985 ◽

1983 ◽

Vol 71 (6) ◽

pp. 985-985

Author(s):

RIF S. EL-MALLAKH

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Protozoan Parasite ◽

Mitochondrial Enzyme ◽

Reye's Syndrome ◽

Electron Microscopic ◽

Microscopic Studies ◽

Mitochondrial Defect ◽

Intracellular Protozoan Parasite

To the Editor.— Mitochondrial failure, manifest by changes in mitochondrial enzyme activity1-3 and morphology,4-5 is central to Reye's syndrome (RS).6 Although it has been variously hypothesized that the mitochondrial changes are secondary to an exogenous toxin,7-12 or an intrinsic mitochondrial defect,6 the actual cause remains obscure. Electron microscopic studies have shown sweelling and loss of cristate in mitochondria of patients with RS. It is interesting that very similar changes occur in Trypanosoma cruzi.13-16 T cruzi is an extracellular/intracellular protozoan parasite which causes Chagas' disease.17

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