Franco R. D’Alessio

Lung transplant for CF: Low lung bacterial burden and immune mediators in year one associate with CLAD development

Samantha A. Whiteside, John E. McGinniss, Rebecca A. Deek, Carter Merenstein et autres

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Macrophage CCL18 promotes lung inflammation in checkpoint inhibitor pneumonitis

Mohammad I. Ghanbar, A.F. Villabona-Rueda, Nicolas Philip, Romy Rodriguez Ortega et autres

BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) is a highly morbid complication of immune checkpoint immunotherapy, characterized by acute lung injury leading, in severe cases, to hypoxic respiratory failure and death. CIP incidence in lung cancer is high (10%-15%). Yet, the pathophysiology of CIP …

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Hypomethylating therapy mitigates acute allograft rejection in a murine lung transplant model

Kristine Yarnoff, W.N. Daccarett-Bojanini, A.F. Villabona-Rueda, Manuel Sollmann et autres

Introduction: Acute cellular rejection of transplanted lung allografts involves activated cytotoxic T cells and reduced Regulatory T (Treg) cell function. Calcineurin inhibitors, the cornerstone of immunosuppressive regimens, suppress T cell cytotoxicity but inhibit Treg proliferation. The DNA hypomethylating agent decitabine (DAC) can …

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SARS-CoV-2 induces neutrophil degranulation and differentiation into myeloid-derived suppressor cells associated with severe COVID-19

Leon L. Hsieh, Elizabeth A. Thompson, Nirvani Jairam, Katerina Roznik et autres

Severe COVID-19 presents with a distinct immunological profile, characterized by elevated neutrophil and reduced lymphocyte counts, seen commonly in fungal and bacterial infections. This study demonstrates that patients hospitalized with COVID-19 show evidence of neutrophil degranulation and have increased expression of neutrophil …

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Combined Effects of Nifedipine and Intermittent Hypoxia on Insulin Signaling Gene Expression and Glucose Homeostasis in Murine Skeletal Muscle

W.K. Berger, Stanley M. Chen Cardenas, Larissa A. Shimoda, Todd A. Baker et autres

Abstract Rationale: Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), alters insulin and glucose homeostasis, contributing to OSA-related adverse physiological effects. Systemic hypertension, frequently co-occurring with OSA, is commonly managed with nifedipine, an L-type calcium channel blocker. However, nifedipine can …

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Exposure to Burn Pit Derivates Leads to Myeloid Dysregulation Towards a Pro-fibrotic Phenotype in Mice

A.F. Villabona-Rueda, W.K. Berger, Trishul Siddharthan, Janeen H. Trembley et autres

Abstract Rationale: Compounds generated from military burn pits including particulate matter, volatile organic compounds, a polycyclic aromatic hydrocarbon have been associated with a range of chronic illnesses including deployment-related constrictive bronchiolitis (DRCB). Furthermore, DRCB is often difficult to diagnose with standard spirometry …

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Impact of Decitabine on Native Lung Immune Profile in a Murine Single-lung Transplant Model

W.N. Daccarett-Bojanini, M. Sollman, Kristine Yarnoff, R. Wang et autres

Abstract Introduction: We previously showed that decitabine (DAC) protects against acute lung graft rejection by impacting adaptive and innate immunity in a murine model. In single-lung transplants, immune responses in the transplanted lung may influence the native lung, though this interaction remains …

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Divergent Immune Resolution Pathways in Murine Models of Pneumonia and Acute Lung Injury: Pathogen-specific Mechanisms of Inflammation and Repair

A.F. Villabona-Rueda, W.N. Daccarett-Bojanini, R. Rodriguez Ortega, W.K. Berger et autres

Abstract Rationale: Pneumonia, a primary cause of acute respiratory distress syndrome (ARDS), drives diverse immune responses based on the infecting agent. Understanding how different pathogens modulate lung inflammation and injury resolution is crucial for developing targeted therapies. Aim: To assess the immunological …

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ICU-Associated Sleep Fragmentation Results in Delayed Lung Injury Recovery Following Pneumonia

Linda Zheng, Aishwarya Magesh, Larissa A. Shimoda, Karthik Suresh et autres

Background: Sleep has long been linked to proper immune system function. Previous studies have shown poor sleep is associated with increased rates of upper respiratory infections; suggesting increased susceptibility to or worsened response to infections. Patients in the ICU experience markedly disrupted …

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Lung Injury Recovery and Cognitive Dysfunction Following Pneumonia: A Role for Sleep Fragmentation

K. Shailaja Ganesh, Linda Zheng, Larissa A. Shimoda, Karthik Suresh et autres

Background: With an approximate of 19% of pneumonia hospitalisations leading to Intensive Care Unit (ICU) admission, an estimated 76 per 100,000 cases of severe pneumonia in the United States require admission to the ICU. Patients with severe pneumonia in the ICU have …

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Proapoptotic Bcl-2 inhibitor as potential host directed therapy for pulmonary tuberculosis

Medha Singh, Mona O. Sarhan, Nerketa N. L. Damiba, Alok Singh et autres

Mycobacterium tuberculosis establishes within host cells by inducing anti-apoptotic Bcl-2 family proteins, triggering necrosis, inflammation, and fibrosis. Here, we demonstrate that navitoclax, an orally bioavailable, small-molecule Bcl-2 inhibitor, significantly improves pulmonary tuberculosis (TB) treatments as a host-directed therapy. Addition of navitoclax to …

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Development of a preclinical model of ICU-associated sleep fragmentation and effects on pneumonia recovery in mice

Mahendra Damarla, Karthik Suresh, Linda Zheng, Kathleen Carino et autres

The study of sleep and its interaction with critical illness has been limited partly due to a paucity of representative models. We developed an ICU-associated sleep fragmentation model that recapitulates many of the key features of sleep experienced by patients in the …

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