Publications by authors named "Kolls J"

Background: Pneumocystis jirovecii pneumonia (PCP) is a leading cause of fungal pneumonia, but its diagnosis primarily relies on invasive bronchoalveolar lavage (BAL) specimens that are difficult to obtain. Oropharyngeal swabs and serum could improve the PCP diagnostic workflow, and we hypothesized that CRISPR could enhance assay sensitivity to allow robust P. jirovecii diagnosis using swabs and serum.

View Article and Find Full Text PDF

Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), is thought to modulate immune responses to viruses.

View Article and Find Full Text PDF

Patients with type 2 and type 1 diabetes (T2D and T1D) exhibit sex-specific differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-sequencing (scRNA-seq) and single nucleus ATAC-sequencing (snATAC-seq) with assays probing hormone secretion and bioenergetics. In non-diabetic (ND) donors, sex differences in islet cell chromatin accessibility and gene expression predominantly involved sex chromosomes.

View Article and Find Full Text PDF
Article Synopsis
  • * Prolonged stress leads to decreased NK cell numbers and functions across various species, with particular age and stress exposure impacting effectiveness; rehabilitation strategies have shown limited success.
  • * Differences in stress response are noted between genders, with females showing greater NK cell suppression, and research indicates mice are not ideal models for studying stress effects on NK cells, pointing to the need for further investigation into the mechanisms behind NK cell dysfunction.
View Article and Find Full Text PDF

Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-Ras) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-Ras uninfected littermates.

View Article and Find Full Text PDF
Article Synopsis
  • Tlr7 deficiency is linked to more severe COVID-19 due to lower production of interferons (IFNs), which are important for the immune response.
  • Infected mice show that the virus activates Tlr7 and IFN pathways initially; however, Tlr7 and Irf7 deficiencies lead to worse symptoms and higher viral loads.
  • Deficiencies in Tlr7 and Irf7 result in reduced antibody production against SARS-CoV-2, hindering the body's ability to clear the virus effectively.
View Article and Find Full Text PDF

Emerging evidence indicates that activation of complement system leading to the formation of the membrane attack complex (MAC) plays a detrimental role in COVID-19. However, their pathogenic roles have never been experimentally investigated before. We used three knock out mice strains (1.

View Article and Find Full Text PDF

Macrophages have been recognized as pivotal players in the progression of MASLD/MASH. However, the molecular mechanisms underlying their multifaceted functions in the disease remain to be further clarified. In the current study, we developed a new mouse model with YAP activation in macrophages to delineate the effect and mechanism of YAP signaling in the pathogenesis of MASLD/MASH.

View Article and Find Full Text PDF

Although the last decade has seen tremendous progress in drugs that treat cystic fibrosis (CF) due to mutations that lead to protein misfolding, there are approximately 8%-10% of subjects with mutations that result in no significant CFTR protein expression demonstrating the need for gene editing or gene replacement with inhaled mRNA or vector-based approaches. A limitation for vector-based approaches is the formation of neutralizing humoral responses. Given that αCD20 has been used to manage post-transplant lymphoproliferative disease in CF subjects with lung transplants, we studied the ability of αCD20 to module both T and B cell responses in the lung to one of the most immunogenic vectors, E1-deleted adenovirus serotype 5.

View Article and Find Full Text PDF

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2.

View Article and Find Full Text PDF

Type 2 and type 1 diabetes (T2D, T1D) exhibit sex differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), hormone secretion, and bioenergetics. In nondiabetic (ND) donors, sex differences in islet cells gene accessibility and expression predominantly involved sex chromosomes.

View Article and Find Full Text PDF

Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant).

View Article and Find Full Text PDF

IL17 is required for the initiation and progression of pancreatic cancer, particularly in the context of inflammation, as previously shown by genetic and pharmacological approaches. However, the cellular compartment and downstream molecular mediators of IL17-mediated pancreatic tumorigenesis have not been fully identified. This study examined the cellular compartment required by generating transgenic animals with IL17 receptor A (IL17RA), which was genetically deleted from either the pancreatic epithelial compartment or the hematopoietic compartment via generation of IL17RA-deficient (IL17-RA-/-) bone marrow chimeras, in the context of embryonically activated or inducible Kras.

View Article and Find Full Text PDF
Article Synopsis
  • * MA30-infected C57BL/6 mice showed severe lung inflammation and edema, similar to what severe COVID-19 patients experience, while K18-ACE2 mice had different inflammation patterns.
  • * The research highlights the importance of T and B cells for an effective immune response against SARS-CoV-2, as their depletion led to worse infection outcomes, whereas NK cells had a minimal effect during the acute phase.
View Article and Find Full Text PDF

Biological sex affects the pathogenesis of type 2 and type 1 diabetes (T2D, T1D) including the development of β cell failure observed more often in males. The mechanisms that drive sex differences in β cell failure is unknown. Studying sex differences in islet regulation and function represent a unique avenue to understand the sex-specific heterogeneity in β cell failure in diabetes.

View Article and Find Full Text PDF

Lung tissue resident memory (TRM) cells are thought to play crucial roles in lung host defense. We have recently shown that immunization with the adjuvant LTA1 (derived from the A1 domain of E. coli heat labile toxin) admixed with OmpX from K.

View Article and Find Full Text PDF
Article Synopsis
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to complex outcomes in children with asthma, whose antiviral immunity could be affected by their condition.
  • This study evaluated SARS-CoV-2 immunity in 53 children with asthma, examining their infection or vaccination history alongside their immune responses to common allergens like dust mites and cockroaches.
  • Results showed that children with atopic asthma had lower antibody responses and neutralization ability against SARS-CoV-2, suggesting that asthma mechanisms might hinder the development of lasting immunity and increase the risk of recurrent infections.
View Article and Find Full Text PDF

T cell immunity, including CD4+ and CD8+ T cell immunity, is critical to host immune responses to infection. Transcriptomic analyses of both CD4+ and CD8+ T cells of C57BL/6 mice show high expression the gene encoding embigin, Emb, which encodes a transmembrane glycoprotein. Moreover, we found that lung CD4+ Th17 tissue-resident memory T cells of C57BL/6 mice also express high levels of Emb.

View Article and Find Full Text PDF

Introduction: The endothelial glycocalyx on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the endothelial glycocalyx. We hypothesized that DMSO would protect against protein leak by preserving the endothelial glycocalyx in a murine model of acute respiratory distress syndrome (ARDS).

View Article and Find Full Text PDF

The calcium-sensing receptor (CaSR), a G protein-coupled receptor, regulates Ca concentration in plasma by regulating parathyroid hormone secretion. In other tissues, it is reported to play roles in cellular differentiation and migration and in secretion and absorption. We reported previously that CaSR can be conditionally deleted in the mouse esophagus.

View Article and Find Full Text PDF

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways.

View Article and Find Full Text PDF
Article Synopsis
  • Respiratory virus infections result in millions of hospitalizations and can lead to long-lasting lung damage and inflammation.
  • A study using C57BL/6 mice infected with influenza showed that the mTORC1 inhibitor rapamycin, when administered after viral clearance, reduced persistent lung inflammation primarily driven by immune cells.
  • The findings suggest that targeting mTORC1 could be a potential treatment for chronic lung inflammation following respiratory viral infections.
View Article and Find Full Text PDF

Microbes influence cancer initiation, progression and therapy responsiveness. IL-17 signaling contributes to gut barrier immunity by regulating microbes but also drives tumor growth. A knowledge gap remains regarding the influence of enteric IL-17-IL-17RA signaling and their microbial regulation on the behavior of distant tumors.

View Article and Find Full Text PDF