Immunology of Infectious Disease Commons^™

Investigating Regulation Of Neutrophil-Mediated Inflammation In Mycoplasma Pneumoniae Infection, Nathan D. Velazquez

University Scholar Projects

No vaccine exists for Mycoplasma pneumoniae (Mp) infections, largely due to the

gap in understanding in the virulence and immunopathogenesis of this bacterium.

We have recently demonstrated that neutrophils are maladaptive in the context of

Mp infection, and drive disease severity while also impairing bacterial clearance.

Furthermore, we observed that B cells play a regulatory role in limiting disease

severity by modulating neutrophilic inflammation. We investigated this

phenomenon further to elucidate the mechanisms by which B cells regulate

neutrophilic inflammation. We utilized a monoclonal antibody to deplete B cells

during Mp infection and found that B-cell-depleted mice had elevated neutrophil …

Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire

Dissertations and Theses (Open Access)

Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …

Antimicrobial Mitochondrial Reactive Oxygen Species Induction By Lung Epithelial Immunometabolic Modulation, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleón García, Miguel M Leiva-Juárez, David L Goldblatt, Fahad Gulraiz, Lisandra Vila Ellis, Jichao Chen, Michael K Longmire, Sri Ramya Donepudi, Philip L Lorenzi, Hao Wang, Lee-Jun Wong, Michael J Tuvim, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs' intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (ΔΨm), differentially modulates ETC complex activities and consequently results in …

Characterization Of A Mycoplasma Pneumoniae Cards Toxin Mutant, Nikaash Pasnoori

Honors Scholar Theses

Mycoplasma pneumoniae is a high-burden pathogen which causes mild to significant infections of the respiratory system. According to the CDC, an estimated two million cases occur yearly in the United States alone, demonstrating the widespread effect of the pathogen. In addition to being the cause of respiratory infections, M. pneumoniae has also been implicated in exacerbating pre-existing asthma conditions. These morbidities make finding a vaccine candidate a vital part of easing the healthcare burden caused by the pathogen. The current mechanism of infection is unknown, but recent evidence points to the Community Acquired Respiratory Distress Syndrome (CARDS) toxin as being …

Mechanism Of Neutrophil Homeostasis And Immunity In Pneumonia And Sepsis, Sagar Paudel

LSU Doctoral Dissertations

Severe bacterial pneumonia and septicemia are pressing health problems. A better understanding of cellular and molecular players of neutrophil immunity and homeostasis in bacterial pneumonia and sepsis is critical for inspiring novel therapeutics. Chemokine CXCL1 is a widely secreted neutrophil attractant and Nod-like receptor (NLRC4) is commonly expressed cytoplasmic pathogen sensor in hematopoietic compartments. How these innate mediators convert pathogen signals into molecular cues of immune response in context of Gram-positive bacterial pneumonia and septicemia largely remain unknown. Utilizing Cxcl1 gene deficient mice, we demonstrate CXCL1 regulates neutrophil influx, bacterial clearance, and host survival in pneumococcal pneumonia-derived sepsis. Furthermore, Cxcl1 …

Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire

LSU Doctoral Dissertations

Acute lower respiratory infections (pneumonia) and pneumonia-derived sepsis are among the leading causes of death in the world causing 7.8 million deaths annually. In this regard, Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the US and implicated for causing high mortality-associated necrotizing pneumonia and aggravating viral pneumonia with superinfection. Additionally, sepsis is the 7^th leading cause of death among newborns in the US and is responsible for more than 750,000 hospitalization cases every year. Although there is a plethora of research in both pneumonia and sepsis, the detailed pathophysiology still remains elusive. Understanding the host defense mechanism will help …