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12 pages, 2170 KiB

Open AccessArticle

Regulation of Serum Exosomal MicroRNAs in Mice Infected with Orientia tsutsugamushi

by Le Jiang, Tatyana Belinskaya, Zhiwen Zhang, Teik-Chye Chan, Wei-Mei Ching and Chien-Chung Chao

Microorganisms 2021, 9(1), 80; https://doi.org/10.3390/microorganisms9010080 - 31 Dec 2020

Cited by 6 | Viewed by 2086

Abstract

Exosomes are small extracellular vesicles that carry proteins, lipids, and nucleic acids. They are circulated in many body fluids and play an important role in intercellular communications. MicroRNAs (miRNAs), as major components of exosomes, are often regulated in many diseases including bacterial and [...] Read more.

Exosomes are small extracellular vesicles that carry proteins, lipids, and nucleic acids. They are circulated in many body fluids and play an important role in intercellular communications. MicroRNAs (miRNAs), as major components of exosomes, are often regulated in many diseases including bacterial and viral infections. Functionally, exosome-carried miRNAs interact with various immune cells and affect their behavior. Little is known whether exosomal miRNAs are regulated during scrub typhus, a potentially lethal infection caused by intracellular bacteria, Orientiatsutsugamushi. In the present study, we utilized a scrub typhus mouse model and collected serum at various time points post infection. A custom quantitative PCR array covering 92 murine miRNAs was used to profile serum exosomal miRNAs. A total of 12 miRNAs were found to be significantly up- or down-regulated at least at one time point post infection when compared to uninfected animals. Further analysis identified multiple miRNAs in the let-7 family that were consistently down-regulated at early and late phase of infection. Functionally, serum exosomes isolated from infected mice displayed strong proinflammatory effect when incubated with bone marrow-derived macrophages. Our data revealed dynamic regulations of serum exosomal miRNA during scrub typhus infection, which could significantly influence host immune responses and disease outcome. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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20 pages, 3054 KiB

Open AccessArticle

Functional Analysis of Two Novel Streptococcus iniae Virulence Factors Using a Zebrafish Infection Model

by Kar Yan Soh, Jacelyn Mei San Loh, Christopher Hall and Thomas Proft

Microorganisms 2020, 8(9), 1361; https://doi.org/10.3390/microorganisms8091361 - 05 Sep 2020

Cited by 9 | Viewed by 3188

Abstract

Streptococcus iniae is a major fish pathogen that contributes to large annual losses in the aquaculture industry, exceeding US$100 million. It is also reported to cause opportunistic infections in humans. We have recently identified two novel S. iniae virulence factors, an extracellular nuclease [...] Read more.

Streptococcus iniae is a major fish pathogen that contributes to large annual losses in the aquaculture industry, exceeding US$100 million. It is also reported to cause opportunistic infections in humans. We have recently identified two novel S. iniae virulence factors, an extracellular nuclease (SpnAi) and a secreted nucleotidase (S5nAi), and verified their predicted enzymatic activities using recombinant proteins. Here, we report the generation of green fluorescent S. iniae spnAi and s5nAi deletion mutants and their evaluation in a transgenic zebrafish infection model. Our results show nuclease and nucleotidase activities in S. iniae could be attributed to SpnAi and S5nAi, respectively. Consistent with this, larvae infected with the deletion mutants demonstrated enhanced survival and bacterial clearance, compared to those infected with wild-type (WT) S. iniae. Deletion of spnAi and s5nAi resulted in sustained recruitment of neutrophils and macrophages, respectively, to the site of infection. We also show that recombinant SpnAi is able to degrade neutrophil extracellular traps (NETs) isolated from zebrafish kidney tissue. Our results suggest that both enzymes play an important role in S. iniae immune evasion and might present potential targets for the development of therapeutic agents or vaccines. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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17 pages, 1948 KiB

Open AccessArticle

Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

by Chintan K. Gandhi, Anatoly N. Mikerov, Faryal Durrani, Todd M. Umstead, Sanmei Hu, Guirong Wang, David S. Phelps and Joanna Floros

Microorganisms 2020, 8(9), 1354; https://doi.org/10.3390/microorganisms8091354 - 04 Sep 2020

Cited by 6 | Viewed by 2520

Abstract

Surfactant protein A (SP-A) plays an important role in innate immunity. The sex-dependent survival of infected SP-A knockout (KO) mice has been observed. Our goal was to study the impact of ozone (O₃) and sex, as well as gonadal hormones, on [...] Read more.

Surfactant protein A (SP-A) plays an important role in innate immunity. The sex-dependent survival of infected SP-A knockout (KO) mice has been observed. Our goal was to study the impact of ozone (O₃) and sex, as well as gonadal hormones, on the bronchoalveolar lavage (BAL) readouts and survival, respectively, of Klebsiella pneumoniae-infected SP-A KO mice. Male and female SP-A KO mice were exposed to O₃ or filtered air and infected with K. pneumoniae. We studied markers of inflammation and tissue damage at 4, 24, and 48 h, as well as the survival over 14 days, of gonadectomized (Gx) mice implanted with control pellets (CoP) or hormone (5α-dihydrotestosterone (DHT) in female gonadectomized mice (GxF) or 17β-estradiol (E₂) in male gonadectomized mice (GxM)). We observed: (1) an increase in neutrophil and macrophage inflammatory protein-2 levels as time progressed post-infection, and O₃ exposure appeared to increase this response; (2) an increase in lactate dehydrogenase, total protein, oxidized protein, and phospholipids in response to O₃ with no consistent sex differences in studied parameters; and (3) a reduction in survival of the GxM and CoP mice, the GxM and E₂ mice, and the GxF and DHT mice but not for the GxF and CoP mice after O₃. Without SP-A, (a) sex was found to have a minimal impact on BAL cellular composition and tissue damage markers, and (b) the impact of gonadal hormones on survival was found to involve different mechanisms than in the presence of SP-A. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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23 pages, 2204 KiB

Open AccessArticle

Impact of Surfactant Protein-A Variants on Survival in Aged Mice in Response to Klebsiella pneumoniae Infection and Ozone: Serendipity in Action

by Nithyananda Thorenoor, David S. Phelps, Padma Kala, Radhika Ravi, Andreas Floros Phelps, Todd M. Umstead, Xuesheng Zhang and Joanna Floros

Microorganisms 2020, 8(9), 1276; https://doi.org/10.3390/microorganisms8091276 - 21 Aug 2020

Cited by 7 | Viewed by 2191

Abstract

Innate immune molecules, SP-A1 (6A², 6A⁴) and SP-A2 (1A⁰, 1A³), differentially affect young mouse survival after infection. Here, we investigated the impact of SP-A variants on the survival of aged mice. hTG mice carried a [...] Read more.

Innate immune molecules, SP-A1 (6A², 6A⁴) and SP-A2 (1A⁰, 1A³), differentially affect young mouse survival after infection. Here, we investigated the impact of SP-A variants on the survival of aged mice. hTG mice carried a different SP-A1 or SP-A2 variant and SP-A-KO were either infected with Klebsiella pneumoniae or exposed to filtered air (FA) or ozone (O₃) prior to infection, and their survival monitored over 14 days. In response to infection alone, no gene- or sex-specific (except for 6A²) differences were observed; variant-specific survival was observed (1A⁰ > 6A⁴). In response to O₃, gene-, sex-, and variant-specific survival was observed with SP-A2 variants showing better survival in males than females, and 1A⁰ females > 1A³ females. A serendipitous, and perhaps clinically important observation was made; mice exposed to FA prior to infection exhibited significantly better survival than infected alone mice. 1A⁰ provided an overall better survival in males and/or females indicating a differential role for SP-A genetics. Improved ventilation, as provided by FA, resulted in a survival of significant magnitude in aged mice and perhaps to a lesser extent in young mice. This may have clinical application especially within the context of the current pandemic. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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13 pages, 1438 KiB

Open AccessArticle

Differential miRNA-Gene Expression in M Cells in Response to Crohn’s Disease-Associated AIEC

by Anaïs Larabi, Laurène Salesse, Charlotte Cordonnier, Lucie Etienne-Mesmin, Nicolas Barnich, Guillaume Dalmasso and Hang Thi Thu Nguyen

Microorganisms 2020, 8(8), 1205; https://doi.org/10.3390/microorganisms8081205 - 07 Aug 2020

Cited by 3 | Viewed by 2307

Abstract

Adherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn’s disease (CD) patients, are able to invade intestinal epithelial cells (IECs) and translocate through M cells overlying Peyer’s patches. The levels of microRNA (miRNA) and gene expression in IECs and M [...] Read more.

Adherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn’s disease (CD) patients, are able to invade intestinal epithelial cells (IECs) and translocate through M cells overlying Peyer’s patches. The levels of microRNA (miRNA) and gene expression in IECs and M cells upon AIEC infection have not been investigated. Here, we used human intestinal epithelial Caco-2 monolayers and an in vitro M-cell model of AIEC translocation to analyze comprehensive miRNA and gene profiling under basal condition and upon infection with the reference AIEC LF82 strain. Our results showed that AIEC LF82 translocated through M cells but not Caco-2 monolayers. Both differential gene expression and miRNA profile in M cells compared to Caco-2 cells were obtained. In addition, AIEC infection induces changes in gene and miRNA profiles in both Caco-2 and M cells. In silico analysis showed that certain genes dysregulated upon AIEC infection were potential targets of AIEC-dysregulated miRNAs, suggesting a miRNA-mediated regulation of gene expression during AIEC infection in Caco-2, as well as M cells. This study facilitates the discovery of M cell-specific and AIEC response-specific gene-miRNA signature and enhances the molecular understanding of M cell biology under basal condition and in response to infection with CD-associated AIEC. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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20 pages, 3874 KiB

Open AccessArticle

Chemically Synthesized Alcaligenes Lipid A Shows a Potent and Safe Nasal Vaccine Adjuvant Activity for the Induction of Streptococcus pneumoniae-Specific IgA and Th17 Mediated Protective Immunity

by Ken Yoshii, Koji Hosomi, Atsushi Shimoyama, Yunru Wang, Haruki Yamaura, Takahiro Nagatake, Hidehiko Suzuki, Huangwenxian Lan, Hiroshi Kiyono, Koichi Fukase and Jun Kunisawa

Microorganisms 2020, 8(8), 1102; https://doi.org/10.3390/microorganisms8081102 - 23 Jul 2020

Cited by 16 | Viewed by 3644

Abstract

Effective and safe vaccine adjuvants are needed to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer’s patch resident Alcaligenes stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific [...] Read more.

Effective and safe vaccine adjuvants are needed to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer’s patch resident Alcaligenes stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific immune responses (including IgA production and Th17 responses) without excessive inflammation. Here, we chemically synthesized Alcaligenes lipid A, the biologically active part of LPS, and examined its efficacy as a nasal vaccine adjuvant for the induction of protectively immunity against Streptococcus pneumoniae infection. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for S. pneumoniae, together with Alcaligenes lipid A. Alcaligenes lipid A supported the generation of high levels of PspA-specific IgA and IgG responses through the augmentation of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, Alcaligenes lipid A promoted PspA-specific CD4⁺ Th17 responses in the CLNs and spleen. Furthermore, neutrophils were recruited to infection sites upon nasal infection and synchronized with the antigen-specific T and B cell responses, resulting in the protection against S. pneumoniae infection. Taken together, Alcaligenes lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by means of augmenting both the innate and acquired arms of mucosal immunity against respiratory bacterial infection. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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Review

Jump to: Research

20 pages, 1774 KiB

Open AccessReview

Innate Lymphoid Cell Plasticity in Mucosal Infections

by Anna A. Korchagina, Ekaterina Koroleva and Alexei V. Tumanov

Microorganisms 2023, 11(2), 461; https://doi.org/10.3390/microorganisms11020461 - 12 Feb 2023

Cited by 7 | Viewed by 2078

Abstract

Mucosal tissue homeostasis is a dynamic process that involves multiple mechanisms including regulation of innate lymphoid cells (ILCs). ILCs are mostly tissue-resident cells which are critical for tissue homeostasis and immune response against pathogens. ILCs can sense environmental changes and rapidly respond by [...] Read more.

Mucosal tissue homeostasis is a dynamic process that involves multiple mechanisms including regulation of innate lymphoid cells (ILCs). ILCs are mostly tissue-resident cells which are critical for tissue homeostasis and immune response against pathogens. ILCs can sense environmental changes and rapidly respond by producing effector cytokines to limit pathogen spread and initiate tissue recovery. However, dysregulation of ILCs can also lead to immunopathology. Accumulating evidence suggests that ILCs are dynamic population that can change their phenotype and functions under rapidly changing tissue microenvironment. However, the significance of ILC plasticity in response to pathogens remains poorly understood. Therefore, in this review, we discuss recent advances in understanding the mechanisms regulating ILC plasticity in response to intestinal, respiratory and genital tract pathogens. Key transcription factors and lineage-guiding cytokines regulate this plasticity. Additionally, we discuss the emerging data on the role of tissue microenvironment, gut microbiota, and hypoxia in ILC plasticity in response to mucosal pathogens. The identification of new pathways and molecular mechanisms that control functions and plasticity of ILCs could uncover more specific and effective therapeutic targets for infectious and autoimmune diseases where ILCs become dysregulated. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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14 pages, 1303 KiB

Open AccessReview

Immune-Based Anti-Staphylococcal Therapeutic Approaches

by Bonggoo Park and George Y. Liu

Microorganisms 2021, 9(2), 328; https://doi.org/10.3390/microorganisms9020328 - 06 Feb 2021

Cited by 5 | Viewed by 2635

Abstract

Widespread methicillin-resistant Staphylococcus aureus (S. aureus) infections within community and healthcare settings are responsible for accelerated development of antibiotic resistance. As the antibiotic pipeline began drying up, alternative strategies were sought for future treatment of S. aureus infections. Here, we review [...] Read more.

Widespread methicillin-resistant Staphylococcus aureus (S. aureus) infections within community and healthcare settings are responsible for accelerated development of antibiotic resistance. As the antibiotic pipeline began drying up, alternative strategies were sought for future treatment of S. aureus infections. Here, we review immune-based anti-staphylococcal strategies that, unlike conventional antibiotics, target non-essential gene products elaborated by the pathogen. These strategies stimulate narrow or broad host immune mechanisms that are critical for anti-staphylococcal defenses. Alternative approaches aim to disrupt bacterial virulence mechanisms that enhance pathogen survival or induce immunopathology. Although immune-based therapeutics are unlikely to replace antibiotics in patient treatment in the near term, they have the potential to significantly improve upon the performance of antibiotics for treatment of invasive staphylococcal diseases. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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22 pages, 2399 KiB

Open AccessReview

Streptococcus gordonii: Pathogenesis and Host Response to Its Cell Wall Components

by Ok-Jin Park, Yeongkag Kwon, Chaeyeon Park, Yoon Ju So, Tae Hwan Park, Sungho Jeong, Jintaek Im, Cheol-Heui Yun and Seung Hyun Han

Microorganisms 2020, 8(12), 1852; https://doi.org/10.3390/microorganisms8121852 - 24 Nov 2020

Cited by 43 | Viewed by 11419

Abstract

Streptococcus gordonii, a Gram-positive bacterium, is a commensal bacterium that is commonly found in the skin, oral cavity, and intestine. It is also known as an opportunistic pathogen that can cause local or systemic diseases, such as apical periodontitis and infective endocarditis. [...] Read more.

Streptococcus gordonii, a Gram-positive bacterium, is a commensal bacterium that is commonly found in the skin, oral cavity, and intestine. It is also known as an opportunistic pathogen that can cause local or systemic diseases, such as apical periodontitis and infective endocarditis. S. gordonii, an early colonizer, easily attaches to host tissues, including tooth surfaces and heart valves, forming biofilms. S. gordonii penetrates into root canals and blood streams, subsequently interacting with various host immune and non-immune cells. The cell wall components of S. gordonii, which include lipoteichoic acids, lipoproteins, serine-rich repeat adhesins, peptidoglycans, and cell wall proteins, are recognizable by individual host receptors. They are involved in virulence and immunoregulatory processes causing host inflammatory responses. Therefore, S.gordonii cell wall components act as virulence factors that often progressively develop diseases through overwhelming host responses. This review provides an overview of S. gordonii, and how its cell wall components could contribute to the pathogenesis and development of therapeutic strategies. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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22 pages, 2596 KiB

Open AccessReview

Innate Lymphoid Cells: Important Regulators of Host–Bacteria Interaction for Border Defense

by Katharina Beck, Hiroshi Ohno and Naoko Satoh-Takayama

Microorganisms 2020, 8(9), 1342; https://doi.org/10.3390/microorganisms8091342 - 02 Sep 2020

Cited by 10 | Viewed by 3294

Abstract

Innate lymphoid cells (ILCs) are a recently discovered type of innate immune lymphocyte. They include three different groups classified by the nature of the transcription factors required for their development and by the cytokines they produce. ILCs mainly reside in tissues close to [...] Read more.

Innate lymphoid cells (ILCs) are a recently discovered type of innate immune lymphocyte. They include three different groups classified by the nature of the transcription factors required for their development and by the cytokines they produce. ILCs mainly reside in tissues close to the mucosal barrier such as the respiratory and gastrointestinal tracts. Due to their close proximity to the mucosal surface, ILCs are exposed to a variety of both commensal and pathogenic bacteria. Under non-pathological conditions, ILCs have been shown to be important regulators for the maintenance of tissue homeostasis by mutual interactions with the microbiome. Besides these important functions at homeostasis, several studies have also provided emerging evidence that ILCs contribute to defense against pathogenic bacterial infection by responding rapidly to the pathogens as well as orchestrating other immune cells. In this review, we summarize recent advances in our understanding of the interactions of ILCs and bacteria, with special focus on the function of the different ILC subsets in bacterial infections. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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22 pages, 3196 KiB

Open AccessReview

Formation and Maturation of the Phagosome: A Key Mechanism in Innate Immunity against Intracellular Bacterial Infection

by Hyo-Ji Lee, Yunseo Woo, Tae-Wook Hahn, Young Mee Jung and Yu-Jin Jung

Microorganisms 2020, 8(9), 1298; https://doi.org/10.3390/microorganisms8091298 - 25 Aug 2020

Cited by 59 | Viewed by 11065

Abstract

Phagocytosis is an essential mechanism in innate immune defense, and in maintaining homeostasis to eliminate apoptotic cells or microbes, such as Mycobacterium tuberculosis, Salmonella enterica, Streptococcus pyogenes and Legionella pneumophila. After internalizing microbial pathogens via phagocytosis, phagosomes undergo a series [...] Read more.

Phagocytosis is an essential mechanism in innate immune defense, and in maintaining homeostasis to eliminate apoptotic cells or microbes, such as Mycobacterium tuberculosis, Salmonella enterica, Streptococcus pyogenes and Legionella pneumophila. After internalizing microbial pathogens via phagocytosis, phagosomes undergo a series of ‘maturation’ steps, to form an increasingly acidified compartment and subsequently fuse with the lysosome to develop into phagolysosomes and effectively eliminate the invading pathogens. Through this mechanism, phagocytes, including macrophages, neutrophils and dendritic cells, are involved in the processing of microbial pathogens and antigen presentation to T cells to initiate adaptive immune responses. Therefore, phagocytosis plays a role in the bridge between innate and adaptive immunity. However, intracellular bacteria have evolved diverse strategies to survive and replicate within hosts. In this review, we describe the sequential stages in the phagocytosis process. We also discuss the immune evasion strategies used by pathogens to regulate phagosome maturation during intracellular bacterial infection, and indicate that these might be used for the development of potential therapeutic strategies for infectious diseases. Full article

(This article belongs to the Special Issue Innate Immunity against Bacterial Infections)

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