Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

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Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response

Microorganisms ◽

10.3390/microorganisms8060824 ◽

2020 ◽

Vol 8 (6) ◽

pp. 824

Author(s):

Antonella Bugatti ◽

Stefania Marsico ◽

Manuela Fogli ◽

Sara Roversi ◽

Serena Messali ◽

...

Keyword(s):

Immune Response ◽

Endothelial Cells ◽

Human Metapneumovirus ◽

Size Exclusion ◽

Microvascular Endothelial Cells ◽

Cytopathic Effects ◽

Viral Particles ◽

Hmpv Infection ◽

Microvascular Endothelial ◽

Tract Infections

Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment.

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Human Metapneumovirus Induces Mucin 19 Which Contributes to Viral Pathogenesis

Pathogens ◽

10.3390/pathogens9090726 ◽

2020 ◽

Vol 9 (9) ◽

pp. 726

Author(s):

Kaitlin McBride ◽

Ma. del Rocio Banos-Lara ◽

Nagarjuna R. Cheemarla ◽

Antonieta Guerrero-Plata

Keyword(s):

Immune Response ◽

Respiratory Tract ◽

Viral Infections ◽

Clinical Symptoms ◽

Human Metapneumovirus ◽

Hmpv Infection ◽

Lower Lung ◽

Tract Infections ◽

Mouse Model Of Infection

Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms to severe bronchiolitis and pneumonia. The production of mucus is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown. Mucins are a major component of mucus and they could have an impact on how the host responds to infections. Using an in vitro system and a mouse model of infection, we identified that Mucin 19 is predominantly expressed in the respiratory tract upon HMPV infection. Moreover, the lack of Muc19 led to an improved disease, lower lung viral titers and a decrease in the number of CD4+ T cells. These data indicate that mucin 19 contributes to the activation of the immune response to HMPV and to HMPV-induced pathogenesis.

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The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.711939 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiangtao Zheng ◽

Weiwei Chen ◽

Fangchen Gong ◽

Ying Chen ◽

Erzhen Chen

Keyword(s):

Immune Response ◽

Organ Dysfunction ◽

Host Response ◽

Therapeutic Targets ◽

Host Immune Response ◽

Unique Form ◽

Pathogen Infection ◽

Programmed Death ◽

Life Threatening ◽

Future Direction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

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Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice

Journal of Virology ◽

10.1128/jvi.80.4.2034-2044.2006 ◽

2006 ◽

Vol 80 (4) ◽

pp. 2034-2044 ◽

Cited By ~ 52

Author(s):

Karen A. Herd ◽

Suresh Mahalingam ◽

Ian M. Mackay ◽

Michael Nissen ◽

Theo P. Sloots ◽

...

Keyword(s):

Young Children ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Human Metapneumovirus ◽

Respiratory Pathogen ◽

Interleukin 12 ◽

Ctl Epitopes ◽

Ctl Epitope ◽

Hmpv Infection ◽

Tract Infections

ABSTRACT Human metapneumovirus (hMPV) has emerged as an important human respiratory pathogen causing upper and lower respiratory tract infections in young children and older adults. In addition, hMPV infection is associated with asthma exacerbation in young children. Recent epidemiological evidence indicates that hMPV may cocirculate with human respiratory syncytial virus (hRSV) and mediate clinical disease similar to that seen with hRSV. Therefore, a vaccine for hMPV is highly desirable. In the present study, we used predictive bioinformatics, peptide immunization, and functional T-cell assays to define hMPV cytotoxic T-lymphocyte (CTL) epitopes recognized by mouse T cells restricted through several major histocompatibility complex class I alleles, including HLA-A*0201. We demonstrate that peptide immunization with hMPV CTL epitopes reduces viral load and immunopathology in the lungs of hMPV-challenged mice and enhances the expression of Th1-type cytokines (gamma interferon and interleukin-12 [IL-12]) in lungs and regional lymph nodes. In addition, we show that levels of Th2-type cytokines (IL-10 and IL-4) are significantly lower in hMPV CTL epitope-vaccinated mice challenged with hMPV. These results demonstrate for the first time the efficacy of an hMPV CTL epitope vaccine in the control of hMPV infection in a murine model.

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The Immune Response to Human Metapneumovirus Is Associated with Aberrant Immunity and Impaired Virus Clearance in BALB/c Mice

Journal of Virology ◽

10.1128/jvi.79.10.5971-5978.2005 ◽

2005 ◽

Vol 79 (10) ◽

pp. 5971-5978 ◽

Cited By ~ 62

Author(s):

Rene Alvarez ◽

Ralph A. Tripp

Keyword(s):

Immune Response ◽

Cytotoxic T Lymphocyte ◽

Adaptive Immune Response ◽

Interleukin 10 ◽

Human Metapneumovirus ◽

Delayed Response ◽

Adaptive Immune ◽

Virus Clearance ◽

Hmpv Infection ◽

Syncytial Virus

ABSTRACT Human metapneumovirus (HMPV), recently identified in isolates from children hospitalized with acute respiratory tract illness, is associated with clinical diagnosis of pneumonia, asthma exacerbation, and acute bronchiolitis in young children. HMPV has been shown to cocirculate with respiratory syncytial virus (RSV) and mediate clinical disease features similarly to RSV. Little is known regarding the pathophysiology or immune response associated with HMPV infection; thus, animal models are needed to better understand the mechanisms of immunity and disease pathogenesis associated with infection. In this study, we examine features of the innate and adaptive immune response to HMPV infection in a BALB/c mouse model. Primary HMPV infection elicits weak innate and aberrant adaptive immune responses characterized by induction of a Th2-type cytokine response at later stages of infection that coincides with increased interleukin-10 expression and persistent virus replication in the lung. Examination of the cytotoxic T lymphocyte and antibody response to HMPV infection revealed a delayed response, but passive transfer of HMPV-specific antibodies provided considerable protection. These features are consistent with virus persistence and indicate that the immune response to HMPV is unique compared to the immune response to RSV.

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Recent advancements of nanomaterial-based therapeutic strategies toward sepsis: bacterial eradication, anti-inflammation, and immunomodulation

Nanoscale ◽

10.1039/d1nr02706a ◽

2021 ◽

Author(s):

Yi Zhao ◽

Minju Pu ◽

Jingwen Zhang ◽

Yanan Wang ◽

Xuefeng Yan ◽

...

Keyword(s):

Immune Response ◽

Organ Dysfunction ◽

Tissue Damage ◽

Host Immune Response ◽

Therapeutic Strategies ◽

Bacterial Eradication ◽

Life Threatening ◽

Anti Inflammation

Sepsis is a life threatening disease that is caused by a dysregulated host immune response to infection, resulting in tissue damage and organ dysfunction, which account for a high in-hospital...

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Clinical Features, Epidemiology, and Climatic Impact of Genotype-specific Human Metapneumovirus Infections: Long-term Surveillance of Hospitalized Patients in South Korea

Clinical Infectious Diseases ◽

10.1093/cid/ciz697 ◽

2019 ◽

Vol 70 (12) ◽

pp. 2683-2694 ◽

Cited By ~ 1

Author(s):

Yong Kwan Lim ◽

Oh Joo Kweon ◽

Hye Ryoun Kim ◽

Tae-Hyoung Kim ◽

Mi-Kyung Lee

Keyword(s):

South Korea ◽

Clinical Characteristics ◽

Large Scale ◽

Sunshine Duration ◽

Meteorological Data ◽

Clinical Manifestations ◽

Human Metapneumovirus ◽

Hmpv Infection ◽

Tract Infections

Abstract Background Human metapneumovirus (hMPV) commonly causes upper and lower respiratory tract infections. Here, we performed long-term retrospective surveillance of hMPV infection among patients hospitalized in South Korea between 2007 and 2016 and investigated seasonal dynamics and clinical characteristics associated with each virus subtype/genotype. Methods Patient specimens were tested for hMPV and other respiratory viruses by commercial molecular assays. Medical records of hMPV-positive patients were reviewed, and hMPV subtype/genotype analysis was performed. We also collected meteorological data and analyzed relationships with hMPV activity. Results Of 23 694 specimens, 1275 (5.4%) were positive; among them, 94.0% were classified into 5 subtypes (A1, A2a, A2b, B1, and B2). Some clinical manifestations differed according to hMPV genotype; however, there was no correlation between hMPV subtype and clinical outcome. Viral activity peaked at 13–20 weeks (April and May) and was associated with climate-specific factors, including temperature, relative humidity, diurnal temperature variation, wind speed, and sunshine duration. Conclusions This large-scale, 10-year study provides valuable information about the clinical characteristics associated with hMPV subtypes and climate factors contributing to virus transmission.

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Autoimmunity in Pulmonary Arterial Hypertension: Evidence for Local Immunoglobulin Production

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.680109 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ting Shu ◽

Yanjiang Xing ◽

Jing Wang

Keyword(s):

Immune Response ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Connective Tissue Diseases ◽

Cell Types ◽

Specific Cell ◽

Virus Infections ◽

Immunoglobulin Production ◽

Life Threatening ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease. The notion that autoimmunity is associated with PAH is widely recognized by the observations that patients with connective tissue diseases or virus infections are more susceptible to PAH. However, growing evidence supports that the patients with idiopathic PAH (IPAH) with no autoimmune diseases also have auto-antibodies. Anti-inflammatory therapy shows less help in decreasing auto-antibodies, therefore, elucidating the process of immunoglobulin production is in great need. Maladaptive immune response in lung tissues is considered implicating in the local auto-antibodies production in patients with IPAH. In this review, we will discuss the specific cell types involved in the lung in situ immune response, the potential auto-antigens, and the contribution of local immunoglobulin production in PAH development, providing a theoretical basis for drug development and precise treatment in patients with PAH.

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Type III interferons disrupt the lung epithelial barrier upon viral recognition

10.1101/2020.05.05.077867 ◽

2020 ◽

Cited By ~ 4

Author(s):

Achille Broggi ◽

Sreya Ghosh ◽

Benedetta Sposito ◽

Roberto Spreafico ◽

Fabio Balzarini ◽

...

Keyword(s):

Immune Response ◽

Viral Infections ◽

Rna Virus ◽

Virus Infections ◽

Highly Pathogenic ◽

Type Iii ◽

Lung Epithelial ◽

Syncytial Virus ◽

Tract Infections ◽

Viral Recognition

AbstractLower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections.

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