Biology subjects

Perez-Lopez, A.

Publications and source records attributed to Perez-Lopez, A..

5 recordsLinked to original sources

bioRxiv2025

Commensal Escherichia coli colonization triggers Peyer's patch development

The gut microbiota plays a pivotal role in shaping mucosal immunity, yet the specific microbes contributing to lymphoid tissue development remain poorly defined. Here, we identify Escherichia coli, a pioneer commensal bacterium, as a key driver of naive B cell accumulation in gut Peyers patches and lamina propria via a CXCR2-dependent mechanism. We show that E. coli promotes B cell recruitment through the production of curli amyloid fibers, which signal via Toll-like receptor 2 (TLR2). Notably, this effect extends beyond the neonatal period, revealing a broader temporal window for microbial modulation of mucosal immune development. These findings reveal a previously unrecognized role for a defined gut commensal bacterium and its molecular products in orchestrating the formation of gut-associated lymphoid tissue and B cell recruitment.

microbiology↗

bioRxiv2024

PgtE protease enables virulent Salmonella to evade C3-mediated serum and neutrophil killing

Non-typhoidal Salmonella serovars, such as Salmonella enterica serovar Typhimurium (STm), are a leading cause of inflammatory diarrhea in otherwise healthy individuals. Among children, the elderly, and immunocompromised individuals, STm can spread to systemic sites and cause potentially lethal bacteremia. Phagocytic cells and the immune complement system are pivotal to preventing the dissemination of STm. PgtE, an STm outer membrane protease, has been previously described to cleave over a dozen mammalian protein substrates in vitro, including complement protein C3. However, these activities have mostly been observed with mutant, avirulent strains with a truncated O-antigen that renders bacteria sensitive to complement killing. Here, we report that virulent STm utilizes PgtE to evade complement-mediated killing in vivo. The wild-type pathogen increases pgtE expression and PgtE proteolytic function within macrophages and in macrophage-like in vitro growth conditions, concomitant with physiologic O-antigen shortening in these environments. Furthermore, we found that wild-type STms resistance to complement-mediated serum and neutrophil killing is PgtE-dependent. We propose that PgtE promotes the systemic spread of STm by acting as a second line of defense against complement when STm escapes from a macrophage.

microbiology↗

bioRxiv2021

Context-aware deconvolution of cell-cell communication with Tensor-cell2cell

Cell interactions determine phenotypes, and intercellular communication is shaped by cellular contexts such as disease state, organismal life stage, and tissue microenvironment. Single-cell technologies measure the molecules mediating cell-cell communication, and emerging computational tools can exploit these data to decipher intercellular communication. However, current methods either disregard cellular context or rely on simple pairwise comparisons between samples, thus limiting the ability to decipher complex cell-cell communication across multiple time points, levels of disease severity, or spatial contexts. Here we present Tensor-cell2cell, an unsupervised method using tensor decomposition, which is the first strategy to decipher context-driven intercellular communication by simultaneously accounting for multiple stages, states, or locations of the cells. To do so, Tensor-cell2cell uncovers context-driven patterns of communication associated with different phenotypic states and determined by unique combinations of cell types and ligand-receptor pairs. As such, Tensor-cell2cell robustly improves upon and extends the analytical capabilities of existing tools. We show Tensor-cell2cell can identify multiple modules associated with distinct communication processes (e.g., participating cell-cell and ligand receptor pairs) linked to COVID-19 severities and Autism Spectrum Disorder. Thus, we introduce an effective and easy-to-use strategy for understanding complex communication patterns across diverse conditions.

bioinformatics↗

bioRxiv2021

CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here we show that CCL28 promotes neutrophil accumulation to the gut of mice infected with Salmonella and to the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency were different between the two infections, as Ccl28-/- mice were highly susceptible to Salmonella gut infection, but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes that were largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not of Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

immunology↗

bioRxiv2019

A Metagenomics - Based Diagnostic Approach for Central Nervous System Infections in Hospital Acute Care Setting

The etiology of central nervous system (CNS) infections such as meningitis and encephalitis remains unknown in a large proportion of cases partly because the diversity of pathogens that may cause CNS infections greatly outnumber available test methods. Here we present a metagenomic next generation sequencing (mNGS) based approach for broad-range detection of pathogens associated with CNS infections, which is suitable for application in the acute care hospital setting. Using an Illumina MiSeq benchtop sequencer and the IDseq pipeline for identifying pathogens in metagenomic sequence data, we show that the analytical sensitivity of mNGS to detect pathogens is comparable to that of PCR in simulated cerebrospinal fluid (CSF) specimens. We then applied this method for pathogen detection in 74 CSF specimens from patients with suspected CNS infections that were previously tested by culture and/or PCR. Diagnostic accuracy, sensitivity and specificity of mNGS approach with reference to conventional methods were all 95%. Furthermore, confirmatory testing on specimens that gave discrepant results were mostly in favor of the mNGS assay. The clinical application of mNGS holds promise to benefit patients with CNS infections of unknown etiology.

pathology↗