Immunopathogenesis of Bacterial Infection

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 27463

Special Issue Editors


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Guest Editor
Department of Medicine, Division of Hematology/Oncology, Department of Immunology and Microbiology, Cancer Center, Rush University Medical Center, Chicago, IL, USA
Interests: pathogen/host interactions; virulence factors; innate immune responses; wound healing; wound infection; diabetic foot ulcer; tumor biology/cancer therapeutics
Department of Microbiology and Immunology, Indiana University School of Medicine-Northwest, Gary, IN 46202, USA
Interests: staphylococcus aureus; signal transduction; antibiotic resistance; drug development

Special Issue Information

Dear Colleagues,

Infection can be caused by a variety of pathogens, including (but not limited to) bacteria. Bacteria can gain entry into our body through wounds, bug bites, or the respiratory tract, where they can colonize and proliferate either intracellularly (within vacuoles or in the cytoplasm) or extracellularly in tissue within host cells. Through the production of a variety of virulence factors, they can impact and shape the host tissue inflammatory environment in such ways to facilitate their pathogenesis. In the past several decades, increasing evidence has revealed that host tissue defenses to bacterial infections depend on early innate immune responses, involving pattern-recognition receptors, canonical and/or non-canonical inflammasomes, cytokines, antimicrobial peptides, inflammatory leukocytes, etc., and adaptive immune responses involving B and T lymphocytes. Therefore, increasing our understanding of the mechanisms of interaction between pathogens and the host immune system is of great significance for early diagnosis, disease occurrence, and treatment.

This Special Issue aims to understand the immunopathogenesis of bacterial infections from a cellular and immunobiological perspective. We invite all scientists working in this area to contribute original research articles, reviews, communications, and short perspective articles on all aspects related to bacterial infection, disease mechanisms and virulence factors, the host-initiated innate and adaptive immune responses, and their pathological and/or beneficial consequences for the host or the infecting pathogen. We particularly welcome articles describing mechanistic insights at the molecular, cellular, or organismal level, as well as those providing translational value.

Prof. Dr. Sasha H. Shafikhani 
Dr. Taeok Bae
Guest Editors

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Keywords

  • bacterial interactions
  • wound infection
  • innate immune responses
  • cell death

Published Papers (10 papers)

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Research

Jump to: Review

22 pages, 2625 KiB  
Article
Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System
by Alfredo Aisa-Álvarez, Israel Pérez-Torres, Verónica Guarner-Lans, Linaloe Manzano-Pech, Randall Cruz-Soto, Ricardo Márquez-Velasco, Sergio Casarez-Alvarado, Juvenal Franco-Granillo, Marcela Elizabeth Núñez-Martínez and María Elena Soto
Cells 2023, 12(9), 1330; https://doi.org/10.3390/cells12091330 - 06 May 2023
Cited by 3 | Viewed by 2207
Abstract
Background and aim: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. Methods: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients [...] Read more.
Background and aim: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. Methods: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. Results: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3/NO2 but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). Conclusions: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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23 pages, 20707 KiB  
Article
lnc001776 Affects CPB2 Toxin-Induced Excessive Injury of Porcine Intestinal Epithelial Cells via Activating JNK/NF-kB Pathway through ssc-let-7i-5p/IL-6 Axis
by Kaihui Xie, Zunqiang Yan, Qiaoli Yang, Xiaoyu Huang, Pengfei Wang, Xiaoli Gao, Jie Li and Shuangbao Gun
Cells 2023, 12(7), 1036; https://doi.org/10.3390/cells12071036 - 29 Mar 2023
Viewed by 1233
Abstract
Piglet diarrhea caused by Clostridium perfringens (C. perfringens) type C (CpC) seriously endangers the development of the pig production industry. C. perfringens beta2 (CPB2) toxin is a virulent toxin produced by CpC. Long non-coding RNAs (lncRNAs) are key [...] Read more.
Piglet diarrhea caused by Clostridium perfringens (C. perfringens) type C (CpC) seriously endangers the development of the pig production industry. C. perfringens beta2 (CPB2) toxin is a virulent toxin produced by CpC. Long non-coding RNAs (lncRNAs) are key regulators in the immune inflammatory response to bacterial infection. Nevertheless, the functional mechanism of lncRNAs in bacterial piglet diarrhea is unclear. Herein, a novel lncRNA lnc001776 expression was confirmed to be substantially elevated in the ileum tissue of CpC-infected diarrhea piglets and in CPB2 toxin-treated porcine small intestinal epithelial cells (IPEC-J2). lnc001776 knockdown restrained CPB2 toxin-induced apoptosis, inflammatory injury, barrier dysfunction and activation of JNK/NF-kB pathway in IPEC-J2 cells. Additionally, ssc-let-7i-5p was identified as sponge for lnc001776. Overexpression of ssc-let-7i-5p repressed CPB2-induced injury in IPEC-J2 cells. Interleukin 6 (IL-6), a target gene of ssc-let-7i-5p, was enhanced in CPB2 toxin-treated IPEC-J2 cells. Rescue experiments demonstrated that a ssc-let-7i-5p mimic reversed the effect of lnc001776 overexpression on CPB2 toxin-induced IPEC-J2 cell injury and JNK/NF-kB pathway, whereas IL-6 overexpression partially restored the impact of lnc001776. Overall, lnc001776 overexpression exacerbated CPB2 toxin-induced IPEC-J2 cell damage by sponging ssc-let-7i-5p to regulate IL-6 to activate JNK/NF-kB pathway, indicating that lnc001776 could be a key target for piglet resistance to CpC-induced diarrhea. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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22 pages, 2709 KiB  
Article
MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia
by Cengiz Goekeri, Peter Pennitz, Wibke Groenewald, Ulrike Behrendt, Holger Kirsten, Christian M. Zobel, Sarah Berger, Gitta A. Heinz, Mir-Farzin Mashreghi, Sandra-Maria Wienhold, Kristina Dietert, Anca Dorhoi, Achim D. Gruber, Markus Scholz, Gernot Rohde, Norbert Suttorp, CAPNETZ Study Group, Martin Witzenrath and Geraldine Nouailles
Cells 2023, 12(6), 959; https://doi.org/10.3390/cells12060959 - 21 Mar 2023
Cited by 2 | Viewed by 2293
Abstract
Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating [...] Read more.
Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary inflammation in wild-type and microRNA-223-knockout mice was assessed in terms of disease course, histopathology, cellular recruitment and evaluation of inflammatory protein and gene signatures following pneumococcal infection. Low levels of serum microRNA-223 correlated with increased disease severity in pneumococcal pneumonia patients. Prolonged neutrophilic influx into the lungs and alveolar spaces was detected in pneumococci-infected microRNA-223-knockout mice, possibly accounting for aggravated histopathology and acute lung injury. Expression of microRNA-223 in wild-type mice was induced by pneumococcal infection in a time-dependent manner in whole lungs and lung neutrophils. Single-cell transcriptome analyses of murine lungs revealed a unique profile of antimicrobial and cellular maturation genes that are dysregulated in neutrophils lacking microRNA-223. Taken together, low levels of microRNA-223 in human pneumonia patient serum were associated with increased disease severity, whilst its absence provoked dysregulation of the neutrophil transcriptome in murine pneumococcal pneumonia. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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18 pages, 2181 KiB  
Article
Host Response of Human Epidermis to Methicillin-Resistant Staphylococcus aureus Biofilm Infection and Synthetic Antibiofilm Peptide Treatment
by Bing (Catherine) Wu, Travis M. Blimkie, Evan F. Haney, Reza Falsafi, Noushin Akhoundsadegh and Robert E. W. Hancock
Cells 2022, 11(21), 3459; https://doi.org/10.3390/cells11213459 - 01 Nov 2022
Cited by 6 | Viewed by 2055
Abstract
Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of [...] Read more.
Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant, and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to methicillin-resistant Staphylococcus aureus (MRSA) biofilm colonization. MRSA biofilm impaired skin barrier function, enhanced extracellular matrix remodelling, elicited inflammatory responses including IL-17, IL-12 family and IL-6 family interleukin signalling, and modulated skin metabolism. Synthetic antibiofilm peptide DJK-5 effectively diminished MRSA biofilm and associated skin inflammation in wounded human ex vivo skin. In the epidermis, DJK-5 shifted the overall skin transcriptome towards homeostasis including modulating the biofilm induced inflammatory response, promoting the skin DNA repair function, and downregulating MRSA invasion of thermally damaged skin. These data clarified the underlying immunopathogenesis of biofilm infections and revealed the intrinsic promise of synthetic peptides in reducing inflammation and biofilm infections. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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13 pages, 2395 KiB  
Article
Bta-miR-223 Targeting the RHOB Gene in Dairy Cows Attenuates LPS-Induced Inflammatory Responses in Mammary Epithelial Cells
by Peng Jiao, Jinpeng Wang, Jian Yang, Xingping Wang and Zhuoma Luoreng
Cells 2022, 11(19), 3144; https://doi.org/10.3390/cells11193144 - 06 Oct 2022
Cited by 4 | Viewed by 1721 | Correction
Abstract
Bovine mammary epithelial cells (bMECs) are part of the first line of defense against pathogens. In recent studies, bta-miR-223 has been reported to activate congenital and innate immunity against inflammatory damage during the pathogenesis of mastitis in dairy cows. The purpose of this [...] Read more.
Bovine mammary epithelial cells (bMECs) are part of the first line of defense against pathogens. In recent studies, bta-miR-223 has been reported to activate congenital and innate immunity against inflammatory damage during the pathogenesis of mastitis in dairy cows. The purpose of this study was to identify the regulatory mechanism of bta-miR-223 and its downstream target genes in inflammatory bMECs. A double luciferase reporter gene assay demonstrated that ras homolog family member B (RHOB) was the target gene of bta-miR-223. To further elucidate the role of bta-miR-223 in congenital immune responses, bta-miR-223 mimics (mimic/inhibitor) were transfected into bMECs stimulated with lipopolysaccharide (LPS), which activates the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway. Real-time quantitative PCR (qPCR) and Western blot were used to detect the expression of related genes and proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect secreted inflammatory factors. Results showed that bta-miR-223 expression during inflammation in bMECs reduced the secretion of inflammatory factors by targeting RHOB and deactivation of NF-κB gene activity. Silencing RHOB inhibited LPS-induced inflammatory response in bMECs. Overall, bta-miR-223 attenuated LPS-induced inflammatory response, and acted as a negative feedback regulator via targeting RHOB, providing a novel avenue for mastitis treatment. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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15 pages, 3827 KiB  
Article
Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection
by Yingjie Wang, Lulu Wang, Fuli Hu, Mengyun Zou, Ronglong Luo, Yingfei Sun, Tengfei Wang, Qiao Guo and Xiuli Peng
Cells 2022, 11(18), 2817; https://doi.org/10.3390/cells11182817 - 09 Sep 2022
Cited by 10 | Viewed by 2137
Abstract
High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory [...] Read more.
High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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Review

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13 pages, 1149 KiB  
Review
Crossing the Barrier: A Comparative Study of Listeria monocytogenes and Treponema pallidum in Placental Invasion
by Samuel J. Eallonardo and Nancy E. Freitag
Cells 2024, 13(1), 88; https://doi.org/10.3390/cells13010088 - 31 Dec 2023
Viewed by 1242
Abstract
Vertically transmitted infections are a significant cause of fetal morbidity and mortality during pregnancy and pose substantial risks to fetal development. These infections are primarily transmitted to the fetus through two routes: (1) direct invasion and crossing the placenta which separates maternal and [...] Read more.
Vertically transmitted infections are a significant cause of fetal morbidity and mortality during pregnancy and pose substantial risks to fetal development. These infections are primarily transmitted to the fetus through two routes: (1) direct invasion and crossing the placenta which separates maternal and fetal circulation, or (2) ascending the maternal genitourinary tact and entering the uterus. Only two bacterial species are commonly found to cross the placenta and infect the fetus: Listeria monocytogenes and Treponema pallidum subsp. pallidum. L. monocytogenes is a Gram-positive, foodborne pathogen found in soil that acutely infects a wide variety of mammalian species. T. pallidum is a sexually transmitted spirochete that causes a chronic infection exclusively in humans. We briefly review the pathogenesis of these two very distinct bacteria that have managed to overcome the placental barrier and the role placental immunity plays in resisting infection. Both organisms share characteristics which contribute to their transplacental transmission. These include the ability to disseminate broadly within the host, evade immune phagocytosis, and the need for a strong T cell response for their elimination. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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20 pages, 3139 KiB  
Review
Chromophore-Targeting Precision Antimicrobial Phototherapy
by Sebastian Jusuf and Pu-Ting Dong
Cells 2023, 12(22), 2664; https://doi.org/10.3390/cells12222664 - 20 Nov 2023
Viewed by 1276
Abstract
Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes [...] Read more.
Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers, like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including protoporphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy’s broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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37 pages, 696 KiB  
Review
Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics
by Stephen J. Wood, Timothy M. Kuzel and Sasha H. Shafikhani
Cells 2023, 12(1), 199; https://doi.org/10.3390/cells12010199 - 03 Jan 2023
Cited by 35 | Viewed by 7252
Abstract
Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many [...] Read more.
Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many of the available antibiotics. In this review, we review the important acute and chronic infections caused by this pathogen. We next discuss various animal models which have been developed to evaluate P. aeruginosa pathogenesis and assess therapeutics against this pathogen. Next, we review current treatments (antibiotics and vaccines) and provide an overview of their efficacies and their limitations. Finally, we highlight exciting literature on novel antibiotic-free strategies to control P. aeruginosa infections. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
33 pages, 2735 KiB  
Review
Pseudomonas aeruginosa Cytotoxins: Mechanisms of Cytotoxicity and Impact on Inflammatory Responses
by Stephen J. Wood, Josef W. Goldufsky, Michelle Y. Seu, Amir H. Dorafshar and Sasha H. Shafikhani
Cells 2023, 12(1), 195; https://doi.org/10.3390/cells12010195 - 03 Jan 2023
Cited by 12 | Viewed by 4535
Abstract
Pseudomonas aeruginosa is one of the most virulent opportunistic Gram-negative bacterial pathogens in humans. It causes many acute and chronic infections with morbidity and mortality rates as high as 40%. P. aeruginosa owes its pathogenic versatility to a large arsenal of cell-associated and [...] Read more.
Pseudomonas aeruginosa is one of the most virulent opportunistic Gram-negative bacterial pathogens in humans. It causes many acute and chronic infections with morbidity and mortality rates as high as 40%. P. aeruginosa owes its pathogenic versatility to a large arsenal of cell-associated and secreted virulence factors which enable this pathogen to colonize various niches within hosts and protect it from host innate immune defenses. Induction of cytotoxicity in target host cells is a major virulence strategy for P. aeruginosa during the course of infection. P. aeruginosa has invested heavily in this strategy, as manifested by a plethora of cytotoxins that can induce various forms of cell death in target host cells. In this review, we provide an in-depth review of P. aeruginosa cytotoxins based on their mechanisms of cytotoxicity and the possible consequences of their cytotoxicity on host immune responses. Full article
(This article belongs to the Special Issue Immunopathogenesis of Bacterial Infection)
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