Serum-mediated activation of macrophages reflects TcVac2 vaccine efficacy against chagas disease

Shivali Gupta, Trevor S. Silva, Jessica E. Osizugbo, Laura Tucker, Heidi Spratt, Nisha Garg

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Chagas disease is endemic in Latin America and an emerging infectious disease in the United States. No effective treatments are available. The TcG1, TcG2, and TcG4 antigens are highly conserved in clinically relevant Trypanosoma cruzi isolates and are recognized by B and T cells in infected hosts. Delivery of these antigens as a DNA prime/protein boost vaccine (TcVac2) elicited lytic antibodies and type 1 CD8+ T cells that expanded upon challenge infection and provided >90% control of parasite burden and myocarditis in chagasic mice. Here we determined if peripheral blood can be utilized to capture the TcVac2-induced protection from Chagas disease. We evaluated the serum levels of T. cruzi kinetoplast DNA (TckDNA), T. cruzi 18S ribosomal DNA (Tc18SrDNA), and murine mitochondrial DNA (mtDNA) as indicators of parasite persistence and tissue damage and monitored the effect of sera on macrophage phenotype. Circulating TckDNA/Tc18SrDNA and mtDNA were decreased by >3- to 5-fold and 2-fold, respectively, in vaccinated infected mice compared to nonvaccinated infected mice. Macrophages incubated with sera from vaccinated infected mice exhibited M2 surface markers (CD16, CD32, CD200, and CD206), moderate proliferation, a low oxidative/nitrosative burst, and a regulatory/anti-inflammatory cytokine response (interleukin-4 [IL-4] plus IL-10 > tumor necrosis factor alpha [TNF-α]). In comparison, macrophages incubated with sera from nonvaccinated infected mice exhibited M1 surface markers, vigorous proliferation, a substantial oxidative/nitrosative burst, and a proinflammatory cytokine response (TNF-α»IL-4 plus IL-10). Cardiac infiltration of macrophages and TNF-α and oxidant levels were significantly reduced in TcVac2-immunized chagasic mice. We conclude that circulating TcDNA and mtDNA levels and macrophage phenotype mediated by serum constituents reflect in vivo levels of parasite persistence, tissue damage, and inflammatory/anti-inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies.

Original languageEnglish (US)
Pages (from-to)1382-1389
Number of pages8
JournalInfection and Immunity
Volume82
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Macrophage Activation
Chagas Disease
Trypanosoma cruzi
Vaccines
Macrophages
Serum
Mitochondrial DNA
Kinetoplast DNA
Respiratory Burst
Tumor Necrosis Factor-alpha
Ribosomal DNA
Interleukin-4
Interleukin-10
Parasites
Anti-Inflammatory Agents
Emerging Communicable Diseases
Cytokines
Communicable Disease Control
T-Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Serum-mediated activation of macrophages reflects TcVac2 vaccine efficacy against chagas disease. / Gupta, Shivali; Silva, Trevor S.; Osizugbo, Jessica E.; Tucker, Laura; Spratt, Heidi; Garg, Nisha.

In: Infection and Immunity, Vol. 82, No. 4, 2014, p. 1382-1389.

Research output: Contribution to journalArticle

Gupta, Shivali ; Silva, Trevor S. ; Osizugbo, Jessica E. ; Tucker, Laura ; Spratt, Heidi ; Garg, Nisha. / Serum-mediated activation of macrophages reflects TcVac2 vaccine efficacy against chagas disease. In: Infection and Immunity. 2014 ; Vol. 82, No. 4. pp. 1382-1389.
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abstract = "Chagas disease is endemic in Latin America and an emerging infectious disease in the United States. No effective treatments are available. The TcG1, TcG2, and TcG4 antigens are highly conserved in clinically relevant Trypanosoma cruzi isolates and are recognized by B and T cells in infected hosts. Delivery of these antigens as a DNA prime/protein boost vaccine (TcVac2) elicited lytic antibodies and type 1 CD8+ T cells that expanded upon challenge infection and provided >90{\%} control of parasite burden and myocarditis in chagasic mice. Here we determined if peripheral blood can be utilized to capture the TcVac2-induced protection from Chagas disease. We evaluated the serum levels of T. cruzi kinetoplast DNA (TckDNA), T. cruzi 18S ribosomal DNA (Tc18SrDNA), and murine mitochondrial DNA (mtDNA) as indicators of parasite persistence and tissue damage and monitored the effect of sera on macrophage phenotype. Circulating TckDNA/Tc18SrDNA and mtDNA were decreased by >3- to 5-fold and 2-fold, respectively, in vaccinated infected mice compared to nonvaccinated infected mice. Macrophages incubated with sera from vaccinated infected mice exhibited M2 surface markers (CD16, CD32, CD200, and CD206), moderate proliferation, a low oxidative/nitrosative burst, and a regulatory/anti-inflammatory cytokine response (interleukin-4 [IL-4] plus IL-10 > tumor necrosis factor alpha [TNF-α]). In comparison, macrophages incubated with sera from nonvaccinated infected mice exhibited M1 surface markers, vigorous proliferation, a substantial oxidative/nitrosative burst, and a proinflammatory cytokine response (TNF-α»IL-4 plus IL-10). Cardiac infiltration of macrophages and TNF-α and oxidant levels were significantly reduced in TcVac2-immunized chagasic mice. We conclude that circulating TcDNA and mtDNA levels and macrophage phenotype mediated by serum constituents reflect in vivo levels of parasite persistence, tissue damage, and inflammatory/anti-inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies.",
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