Abstract

During histoplasmosis, Histoplasma capsulatum soluble antigens (CFAg) can be naturally released by yeast cells. Because CFAg can be specifically targeted during infection, in the present study we investigated CFAg release in experimental murine histoplasmosis, and evaluated the host humoral immune response against high-molecular-mass antigens (hMMAg. >150 kDa), the more immunogenic CFAg fraction. Mice were infected with 2.2 x 10⁴ H. capsulatum IMT/HC128 yeast cells. The soluble CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg circulating immune complexes (CIC) levels were determined by enzymelinked immunosorbent assay, at days 0, 7, 14, and 28 post-infection. We observed a progressive increase in circulating levels of CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg CIC after H. capsulatum infection. The hMMAg showed a high percentage of carbohydrates and at least two main immunogenic components. We verified for the first time that hMMAg from H. capsulatum IMT/HC128 strain induce humoral immune response and lead to CIC formation during experimental histoplasmosis.

Highlights

  • During histoplasmosis, Histoplasma capsulatum soluble antigens (CFAg) can be naturally released by yeast cells

  • Our results show for the first time evidence that H. capsulatum cellfree antigens (CFAg) or highmolecular-mass antigens (hMMAg) are released during experimental infection and induce humoral immune response and formation of circulating immune complexes (CIC)

  • To evaluate whether H. capsulatum IMT/HC128 cell-free antigens are produced after IMT/HC128 infection, we measured CFAg level in the serum from infected mice during experimental histoplasmosis

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Summary

Introduction

Histoplasma capsulatum soluble antigens (CFAg) can be naturally released by yeast cells. Because CFAg can be targeted during infection, in the present study we investigated CFAg release in experimental murine histoplasmosis, and evaluated the host humoral immune response against high-molecular-mass antigens Methods: Mice were infected with 2.2x104 H. capsulatum IMT/HC128 yeast cells. The soluble CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg circulating immune complexes (CIC) levels were determined by enzymelinked immunosorbent assay, at days 0, 7, 14, and 28 post-infection. Results: We observed a progressive increase in circulating levels of CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg CIC after H. capsulatum infection. Conclusions: We verified for the first time that hMMAg from H. capsulatum IMT/HC128 strain induce humoral immune response and lead to CIC formation during experimental histoplasmosis. Fungal replication can be reactivated from latent foci if the integrity of the host’s immune system is impaired[1,4,5,6]

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