Decoding communication patterns of the innate immune system by quantitative proteomics

Abstract

The innate immune system is a collective network of cell types involved in cell recruitment and activation using a robust and refined communication system. Engagement of receptor-mediated intracellular signaling initiates communication cascades by conveying information about the host cell status to surrounding cells for surveillance and protection. Comprehensive profiling of innate immune cells is challenging due to low cell numbers, high dynamic range of the cellular proteome, low abundance of secreted proteins, and the release of degradative enzymes (e.g., proteases).However, recent advances in mass spectrometry-based proteomics provides the capability to overcome these limitations through profiling the dynamics of cellular processes, signaling cascades, post-translational modifications, and interaction networks. Moreover, integration of technologies and molecular datasets provide a holistic view of a complex and intricate network of communications underscoring host defense and tissue homeostasis mechanisms. In this Review, we explore the diverse applications of mass spectrometry-based proteomics in innate immunity to define communication patterns of the innate immune cells during health and disease. We also provide a technical overview of mass spectrometry-based proteomic workflows, with a focus on bottom-up approaches, and we present the emerging role of proteomics in immune-based drug discovery while providing a perspective on new applications in the future.

Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production

“…Macrophages are found ubiquitously throughout the body and are often an early responder to bacterial infection. The interaction between macrophages and K. pneumoniae present a well-studied system to explore the relationship between host and pathogen under in vitro settings [43][44][45][46]. Macrophage cytotoxicity assays showed that deletion of chaB (leading to reduced capsule size) impacts bacterial virulence.…”

Mass Spectrometry Advances and Perspectives for the Characterization of Emerging Adoptive Cell Therapies

“…Fundamental proteomic research has unearthed a wealth of knowledge pertaining to disease pathways, identification of disease markers, and drug targets for the remediation of these studied diseases [4]. Proteomic studies of the human innate immune system have also become increasingly important to understanding the complex signaling patterns involved in responding to diseases [5]. For example, MS-based phosphoproteomics has identified signaling pathways and specific proteins that are involved in the maturation of primary T-cells [6,7] and the function of cytotoxic T-lymphocytes [8].…”

Quantitative Proteomic Profiling of Murine Ocular Tissue and the Extracellular Environment

“…The information obtained from quantitative proteomic profiling can inform treatment strategies, patient stratification, molecular mechanisms underpinning phenotypic observations and details pertaining to signaling networks, and protein-protein interactions critical to the evaluated criteria (Mann, Kulak, Nagaraj, & Cox, 2013). In addition, proteomic profiling can provide valuable insight into the interplay between host and pathogen during infection and generate large datasets outlining changes from these dual perspectives in a single experiment (Ball, Bermas, Carruthers-Lay, & Geddes-McAlister, 2019;Jean Beltran, Federspiel, Sheng, & Cristea, 2017;Sukumaran et al, 2019). For example, proteomic profiling of the ocular surface during infection with Pseudomonas aeruginosa, a Gramnegative bacterial pathogen and the primary causative agent of ocular keratitis, defines global and site-specific host responses to infection and uncovers potential biomarkers for prognostic and diagnostic purposes (Yeung, Gadjeva, & Geddes-McAlister, 2020).…”