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Open AccessArticle

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

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

J. Fungi 2021, 7(11), 938; https://doi.org/10.3390/jof7110938 - 4 Nov 2021

Cited by 9 | Viewed by 2850

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. Full article

(This article belongs to the Special Issue Histoplasma and Histoplasmosis 2020)

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17 pages, 1948 KB

Open AccessArticle

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

by Chintan K. Gandhi, Anatoly N. Mikerov, Faryal Durrani, Todd M. Umstead, Sanmei Hu, Guirong Wang, David S. Phelps and Joanna Floros

Microorganisms 2020, 8(9), 1354; https://doi.org/10.3390/microorganisms8091354 - 4 Sep 2020

Cited by 6 | Viewed by 3439

Abstract

Surfactant protein A (SP-A) plays an important role in innate immunity. The sex-dependent survival of infected SP-A knockout (KO) mice has been observed. Our goal was to study the impact of ozone (O₃) and sex, as well as gonadal hormones, on the bronchoalveolar lavage (BAL) readouts and survival, respectively, of Klebsiella pneumoniae-infected SP-A KO mice. Male and female SP-A KO mice were exposed to O₃ or filtered air and infected with K. pneumoniae. We studied markers of inflammation and tissue damage at 4, 24, and 48 h, as well as the survival over 14 days, of gonadectomized (Gx) mice implanted with control pellets (CoP) or hormone (5α-dihydrotestosterone (DHT) in female gonadectomized mice (GxF) or 17β-estradiol (E₂) in male gonadectomized mice (GxM)). We observed: (1) an increase in neutrophil and macrophage inflammatory protein-2 levels as time progressed post-infection, and O₃ exposure appeared to increase this response; (2) an increase in lactate dehydrogenase, total protein, oxidized protein, and phospholipids in response to O₃ with no consistent sex differences in studied parameters; and (3) a reduction in survival of the GxM and CoP mice, the GxM and E₂ mice, and the GxF and DHT mice but not for the GxF and CoP mice after O₃. Without SP-A, (a) sex was found to have a minimal impact on BAL cellular composition and tissue damage markers, and (b) the impact of gonadal hormones on survival was found to involve different mechanisms than in the presence of SP-A. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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23 pages, 2204 KB

Open AccessArticle

Impact of Surfactant Protein-A Variants on Survival in Aged Mice in Response to Klebsiella pneumoniae Infection and Ozone: Serendipity in Action

by Nithyananda Thorenoor, David S. Phelps, Padma Kala, Radhika Ravi, Andreas Floros Phelps, Todd M. Umstead, Xuesheng Zhang and Joanna Floros

Microorganisms 2020, 8(9), 1276; https://doi.org/10.3390/microorganisms8091276 - 21 Aug 2020

Cited by 8 | Viewed by 3159

Abstract

Innate immune molecules, SP-A1 (6A², 6A⁴) and SP-A2 (1A⁰, 1A³), differentially affect young mouse survival after infection. Here, we investigated the impact of SP-A variants on the survival of aged mice. hTG mice carried a different SP-A1 or SP-A2 variant and SP-A-KO were either infected with Klebsiella pneumoniae or exposed to filtered air (FA) or ozone (O₃) prior to infection, and their survival monitored over 14 days. In response to infection alone, no gene- or sex-specific (except for 6A²) differences were observed; variant-specific survival was observed (1A⁰ > 6A⁴). In response to O₃, gene-, sex-, and variant-specific survival was observed with SP-A2 variants showing better survival in males than females, and 1A⁰ females > 1A³ females. A serendipitous, and perhaps clinically important observation was made; mice exposed to FA prior to infection exhibited significantly better survival than infected alone mice. 1A⁰ provided an overall better survival in males and/or females indicating a differential role for SP-A genetics. Improved ventilation, as provided by FA, resulted in a survival of significant magnitude in aged mice and perhaps to a lesser extent in young mice. This may have clinical application especially within the context of the current pandemic. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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18 pages, 4820 KB

Open AccessArticle

Staphylococcus aureus Lung Infection Results in Down-Regulation of Surfactant Protein-A Mainly Caused by Pro-Inflammatory Macrophages

by Elisabeth Schicke, Zoltán Cseresnyés, Knut Rennert, Vanessa Vau, Karoline Frieda Haupt, Franziska Hornung, Sandor Nietzsche, Fatina Swiczak, Michaela Schmidtke, Brigitte Glück, Mirijam Koch, Michael Schacke, Regine Heller, Alexander S. Mosig, Marc Thilo Figge, Christina Ehrhardt, Bettina Löffler and Stefanie Deinhardt-Emmer

Microorganisms 2020, 8(4), 577; https://doi.org/10.3390/microorganisms8040577 - 16 Apr 2020

Cited by 24 | Viewed by 6838

Abstract

Pneumonia is the leading cause of hospitalization worldwide. Besides viruses, bacterial co-infections dramatically exacerbate infection. In general, surfactant protein-A (SP-A) represents a first line of immune defense. In this study, we analyzed whether influenza A virus (IAV) and/or Staphylococcus aureus (S. aureus) infections affect SP-A expression. To closely reflect the situation in the lung, we used a human alveolus-on-a-chip model and a murine pneumonia model. Our results show that S. aureus can reduce extracellular levels of SP-A, most likely attributed to bacterial proteases. Mono-epithelial cell culture experiments reveal that the expression of SP-A is not directly affected by IAV or S. aureus. Yet, the mRNA expression of SP-A is strongly down-regulated by TNF-α, which is highly produced by professional phagocytes in response to bacterial infection. By using the human alveolus-on-a-chip model, we show that the down-regulation of SP-A is strongly dependent on macrophages. In a murine model of pneumonia, we can confirm that S. aureus decreases SP-A levels in vivo. These findings indicate that (I) complex interactions of epithelial and immune cells induce down-regulation of SP-A expression and (II) bacterial mono- and super-infections reduce SP-A expression in the lung, which might contribute to a severe outcome of bacterial pneumonia. Full article

(This article belongs to the Special Issue Microbe–Host Interactions: From Infection to Innate Immunity Aspects)

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