Biology subjects

Gower, M. S.

Publications and source records attributed to Gower, M. S..

4 recordsLinked to original sources

bioRxiv2026

PIM6 Induces Tolerance and Confers Protection against Mycobacterium tuberculosis in Primary Macrophages

Glycolipids are major components of the mycobacterial cell envelope and play critical roles in host-pathogen interactions. Here we investigate the capacity of the mycobacterial glycolipid phosphatidyl-myo-inositol hexamannosides (PIM6) to modulate innate responsiveness in naive primary human monocytes and monocyte-derived macrophages (MDMs). Monocytes and MDMs prestimulated with PIM6, followed by 5 days of rest, secreted attenuated levels of tumor necrosis factor alpha (TNF-), interleukin 6 (IL-6), and interleukin 10 (IL-10) following LPS challenge. PIM6 pretreatment significantly altered pattern recognition receptor expression through the experimental time course and programmed a tolerized phenotype in myeloid cells independent of TLR2 activity. In an infection challenge with H37Rv Mycobacterium tuberculosis (M.tb), MDMs pretreated with PIM6 secreted decreased levels of TNF- and IL-10 and exhibited early increased bacterial control. Together, these data reveal PIM6 as a complex immunomodulator that tolerizes myeloid cells to subsequent stimuli and exerts direct effects on the control of M.tb infection.

immunology↗

bioRxiv2025

Previous malaria exposure attenuates monocyte-driven inflammation and shapes B cell immunity

Clinical immunity to malaria develops after repeated malaria episodes. In this process, the inflammatory response is modulated to respond less vigorously upon reinfection. Monocytes are a major source of pro-inflammatory mediators during blood-stage infection and are known to adapt to repeated pathogen exposure. Here, we investigated the impact of previous malaria exposure on monocytes during blood-stage malaria by comparing the response in previously exposed and primary infected individuals. We observed reduced levels of the proinflammatory chemokine CXCL10 in previously exposed individuals, linked to changes in CD16+ monocytes. Similarly, BAFF levels were lower in these individuals and associated with modulation of monocyte and dendritic cells. This affected the BAFF-BAFF-R axis, crucial for B cell responses, correlating with increasing parasite-specific antibody levels. Collectively, we present novel insights into how previous malaria exposure shapes monocyte responses during acute malaria and how these in turn correlate with modulation of the B cell compartment and humoral immune response.

immunology↗

bioRxiv2024

IMMUNOPHENOTYPING AND FUNCTIONAL ANALYSIS OF NK CELL SUBSETS IN Mycobacterium tuberculosis-INFECTED INDIVIDUALS

Infection with Mycobacterium tuberculosis remains a global health challenge, with diverse clinical outcomes ranging from latent TB (LTB) infection to active TB disease (ATB). We conducted a comprehensive analysis of NK cell subsets and function in individuals with LTB, ATB, and healthy controls to elucidate their potential association with TB pathogenesis. Peripheral blood mononuclear cells (PBMCs) were isolated from Mtb-infected individuals and analyzed by mass cytometry and flow cytometry. We identified distinct NK cell subsets and evaluated their functional responses to stimulation. Our findings revealed comparable frequencies of total and NK cell subsets across LTB, ATB, and controls. Functional assays demonstrated similar degranulation, cytokine production, and proliferation capabilities among NK cell subsets across the three groups. This study provides insights into the heterogeneity of NK cell responses in TB and highlights the need for standardized methodologies with well-characterized cohorts controlling for donor background. Further investigations are warranted to delineate the specific roles of NK cells in TB immunity and pathogenesis.

immunology↗

bioRxiv2020

A modular microscale granuloma model for immune-microenvironment signaling studies in vitro

Tuberculosis (TB) is one of the most potent infectious diseases in the world, causing more deaths than any other single infectious agent. TB infection is caused by inhalation of Mycobacterium tuberculosis (Mtb) and subsequent phagocytosis and migration into the lung tissue by innate immune cells (e.g., alveolar macrophages, neutrophils, dendritic cells), resulting in the formation of a fused mass of immune cells known as the granuloma. Considered the pathological hallmark of TB, the granuloma is a complex microenvironment that is crucial for pathogen containment as well as pathogen survival. Disruption of the delicate granuloma microenvironment via numerous stimuli, such as variations in cytokine secretions, nutrient availability, and the makeup of immune cell population, can lead to an active infection. Herein, we present a novel in vitro model to examine the soluble factor signaling between a mycobacterial infection and its surrounding environment. Adapting a newly developed suspended microfluidic platform, known as Stacks, we established a modular microscale infection model containing human immune cells and a model mycobacterial strain that can easily integrate with different microenvironmental cues through simple spatial and temporal "stacking" of each module of the platform. We validate the establishment of suspended microscale (4 L) infection cultures that secrete increased levels of proinflammatory factors IL-6, VEGF, and TNF upon infection and form 3D aggregates (granuloma model) encapsulating the mycobacteria. As a proof of concept to demonstrate the capability of our platform to examine soluble factor signaling, we cocultured an in vitro angiogenesis model with the granuloma model and quantified morphology changes in endothelial structures as a result of culture conditions (P < 0.05 when comparing infected vs. uninfected coculture systems). We envision our modular in vitro granuloma model can be further expanded and adapted for studies focusing on the complex interplay between granulomatous structures and their surrounding microenvironment, as well as a complementary tool to augment in vivo signaling and mechanistic studies.

bioengineering↗