Detection of Cytokines and Collectins in Bronchoalveolar Fluid Samples of Patients Infected with Histoplasma capsulatum and Pneumocystis jirovecii.

Laura E Carreto-Binaghi,José-Arturo Martínez-Orozco,Edgar Zenteno,Maria-Lucia Taylor,Eda P Tenorio,El Moukhtar Aliouat,Fernando R Morales-Villarreal

doi:10.3390/jof7110938

Abstract

Histoplasmosis and pneumocystosis co-infections have been reported mainly in immunocompromised humans and in wild animals. The immunological response to each fungal infection has been described primarily using animal models; however, the host response to concomitant infection is unknown. The present work aimed to evaluate the pulmonary immunological response of patients with pneumonia caused either by Histoplasma capsulatum, Pneumocystis jirovecii, or their co-infection. We analyzed the pulmonary collectin and cytokine patterns of 131 bronchoalveolar lavage samples, which included HIV and non-HIV patients infected with H. capsulatum, P. jirovecii, or both fungi, as well as healthy volunteers and HIV patients without the studied fungal infections. Our results showed an increased production of the surfactant protein-A (SP-A) in non-HIV patients with H. capsulatum infection, contrasting with HIV patients (p < 0.05). Significant differences in median values of SP-A, IL-1β, TNF-α, IFN-γ, IL-18, IL-17A, IL-33, IL-13, and CXCL8 were found among all the groups studied, suggesting that these cytokines play a role in the local inflammatory processes of histoplasmosis and pneumocystosis. Interestingly, non-HIV patients with co-infection and pneumocystosis alone showed lower levels of SP-A, IL-1β, TNF-α, IFN-γ, IL-18, IL-17A, and IL-23 than histoplasmosis patients, suggesting an immunomodulatory ability of P. jirovecii over H. capsulatum response.

Highlights

IntroductionReports on Histoplasma capsulatum and Pneumocystis sp
surfactant protein-A (SP-A) median values were higher in most groups of infected patients (H. capsulatum, P. jirovecii, or co-infection) and statistical significance (p = 0.0007) was found among the eight groups of individuals studied (Figure 2)
Based on their critical roles in lung immunity, we investigated the levels of SP-A and SP-D in Bronchoalveolar Lavage (BAL) samples from patients with H. capsulatum and P. jirovecii pneumonia and, for the first time, in patients co-infected with both fungi we searched for associations between the production of these collectins and these fungal infections

Summary

Introduction

Reports on Histoplasma capsulatum and Pneumocystis sp. Co-infection in wild animals [1,2]. Humans [3,4,5,6,7,8,9] are scarce, especially in immunocompromised patients, and both mycoses are AIDS-defining conditions [10]. H. capsulatum is a dimorphic fungus that causes histoplasmosis, one of the most common human respiratory mycoses. The aerosolized infective mycelial phase propagules of H. capsulatum are the source of infection for mammalian hosts in the environment and, in the infected host, the fungus converts into a parasitic and virulent yeast phase [16]

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