Immunotherapy for Fungal Infections

Opportunistic fungal infections are a major health problem being appointed by some studies as the fourth main cause of hospital-acquired infection in susceptible populations. The constantly growing incidences of these diseases are associated with the growing number of susceptible individuals, such as immunocompromised individuals (leukemia, AIDS, etc) and treatment-induced immunodeficiency (hematopoietic stem cell, solid organ transplant, anticancer therapy). Furthermore, other advances in medical care, patient’s long-term hospitalization and antimicrobial therapies have created several vulnerable populations to fungal infections. Currently, antifungal drug therapies are several times inefficient, and the poor outcomes are linked to difficulties in the early diagnosis of fungal infections and drug resistance among fungal pathogens. In this context, novel therapeutic approaches are welcome to stimulate efficiently the host immune response to eliminate the fungal pathogen. This chapter is intended to review advances in immunotherapy strategies for fungal infections

Evolution of subcutaneous lesions of immunocompetent BALB/c mice experimentally infected by the subcutaneous route with 2 x 10⁴ <i>P</i>. <i>insidiosum</i> zoospores (PI group).

<p>A) ulcerative lesions eight days after infection (the lesion was humidified with sterile water for better visualization); B) the same mouse from Fig 1A with spontaneous resolution of the ulcerative lesion 10 days after infection.</p

Survival rates of uninfected immunocompetent (Control, <i>n</i> = 5), infected immunocompetent (PI, <i>n</i> = 5) and immunosuppressed mice with one dose of 200 mg/Kg cyclophosphamide plus one dose of 250 mg/Kg hydrocortisone acetate at 72 h and 24 h, respectively, before infection (PI+CYP+HCA, <i>n</i> = 20).

<p>Mice were infected by the subcutaneous route with 2 x 10⁴ <i>P</i>. <i>insidiosum</i> zoospores. The 14-day survival rate was 100% for Control and PI groups and 40.0% for the CYP+HCA group (<i>p</i> < 0.001; log-rank test). Control and PI groups are superimposed on the first line.</p

Histological lesions and immunohistochemistry of pythiosis in the kidneys, liver and lungs of BALB/c mice from the immunosuppressed (PI+CYP+HCA) group that was subcutaneously infected with <i>P</i>. <i>insidiosum</i>.

<p>A) Histological sections of kidney from a healthy control mouse (hematoxylin-eosin [HE, Bar = 20μm]). B) Kidney sections from the infected mouse with thrombosis (arrow) and tubular necrosis (arrowheads) (HE, Bar = 20μm). C) Positively stained hyphae are observed in the arterial small thrombus and vessel wall and surrounding the kidney (arrowheads) (immunohistochemistry [IHC] anti-<i>P</i>. <i>insidiosum</i>, peroxidase-polymer method, Bar = 20 μm). D) Histological sections of liver from a healthy control mouse (HE, Bar = 20 μm). E) Liver of the infected mouse with thrombus (arrow) containing negative profiles of hyphae (arrowheads) (HE, Bar = 20 μm). F) Positively stained hyphae are observed in the arterial thrombus and vessel wall and surrounding the liver (arrowheads) (IHC anti-<i>P</i>. <i>insidiosum</i>, Bar = 20 μm). G) Histological sections of the lung from a healthy control mouse (HE, Bar = 50 μm). H) Lung with severe congestion in septal capillaries and multifocal hemorrhage (arrowhead) in alveoli with mild edema (arrow) and fibrin (HE Bar = 20 μm). I) Lung with fibrinoid necrosis (arrow) and thrombosis (arrowhead) in one arteriole (HE, Bar = 20 μm).</p