Contributions of maternal and fetal antiviral immunity in congenital disease

Science ◽  
2020 ◽  
Vol 368 (6491) ◽  
pp. 608-612 ◽  
Author(s):  
Laura J. Yockey ◽  
Carolina Lucas ◽  
Akiko Iwasaki
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Immune Defense ◽  
Congenital Disease ◽  
Fetal Demise ◽  
Developmental Defects ◽  
Maternal Immune Activation

Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.

scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

scholarly journals Dengue Virus and the Relationship with MicroRNAs

2020 ◽  
Author(s):  
Samir Casseb ◽  
Karla de Melo
Keyword(s):  
Dengue Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Defense ◽  
Tropical Regions ◽  
Denv Serotypes ◽  
History Of ◽  
Infection Processes ◽  
The Relationship

Dengue is an acute febrile disease caused by a virus of the genus Flavivirus, family Flaviviridae, endemic in tropical regions of the globe. The agent is a virus with single-stranded RNA, classified into four distinct dengue virus (DENV) serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The host’s innate and adaptive immune responses play an essential role in determining the natural history of viral infections, especially in dengue. In this context, it has observed in recent years that the presence of RNA interference (RNAi) in viral infection processes is increasing, as well as immune defense. The context microRNAs (miRNAs) go for stood out, as their presence during viral infection, both in the replication of the virus and in the defense against these infections, becomes increasingly noticeable, therefore, making it increasingly necessary to better understand the role of these small RNAs within viral infection by DENV and what their consequences are in aggravating the consequences of patients affected by this disease.

scholarly journals Sex differences in severity and mortality from COVID-19: are males more vulnerable?

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajay Pradhan ◽  
Per-Erik Olsson
Keyword(s):  
Sex Differences ◽  
Immune System ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Basic Research ◽  
Contributing Factors ◽  
High Infection ◽  
Males And Females

Abstract Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

scholarly journals The Role of IL-33 in Host Response toCandida albicans

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
C. Rodríguez-Cerdeira ◽  
A. Lopez-Bárcenas ◽  
B. Sánchez-Blanco ◽  
R. Arenas
Keyword(s):  
Defense Mechanisms ◽  
Fungal Pathogens ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Case Reports ◽  
Pathogenic Fungi ◽  
Cell Types ◽  
Immune Defense ◽  
Beneficial Role

Background. Interleukin (IL) 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses.Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system followingCandida albicanscolonization. Our literature review included cross-references from retrieved articles and specific data from our own studies.Results. IL-33 (IL-1F11) is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, includingC. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections byCandidaspp.Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.

scholarly journals The Role of Porphyromonas gingivalis Virulence Factors in Periodontitis Immunopathogenesis

2020 ◽  
Vol 23 (1) ◽  
pp. 6-12
Author(s):  
Tienneke Riana Septiwidyati ◽  
Endang Winiati Bachtiar
Keyword(s):  
Immune Responses ◽  
Porphyromonas Gingivalis ◽  
Virulence Factors ◽  
Defense Mechanisms ◽  
Tooth Loss ◽  
Innate Immune ◽  
Not Given ◽  
Innate Immune Responses ◽  
Oral Bacterium

Porphyromonas gingivalis is an anaerobic Gram-negative oral bacterium involved in the pathogenesis of periodontitis. Periodontitis is an infection that is characterized by damage to the supporting tissues of the teeth so that it can cause tooth loss if not given treatment. P. gingivalis locally can invade periodontal tissue and avoid host defense mechanisms. This bacterium has virulence factors which can cause deregulation of innate immune responses and inflammation in the host. The role of P. gingivalis virulence factors such as capsules, fimbriae, lipopolysaccharides, and gingipain in the pathogenesis of periodontitis will be discussed in this paper.

scholarly journals MiR-146a in Immunity and Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Nicole Rusca ◽  
Silvia Monticelli
Keyword(s):  
Immune Responses ◽  
Recent Progress ◽  
Viral Infections ◽  
Cellular Functions ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Different Types ◽  
A Cell ◽  
And Function

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease.

scholarly journals Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons

2020 ◽  
Author(s):  
Daisy X. Ji ◽  
Kristen C. Witt ◽  
Dmitri I. Kotov ◽  
Shally R. Margolis ◽  
Alexander Louie ◽  
...  
Keyword(s):  
Immune Responses ◽  
Legionella Pneumophila ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Transcriptional Regulator ◽  
Type I Interferons ◽  
Type I ◽  
Viral Immunity ◽  
Type I Ifns

AbstractType I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. How type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections, remains poorly understood. The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to many bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that functions to repress the expression of type I IFNs during bacterial infections. We generated Sp140−/− mice and find they are susceptible to infection by diverse bacteria, including Listeria monocytogenes, Legionella pneumophila, and Mycobacterium tuberculosis. Susceptibility of Sp140−/− mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (Ifnar−/−). Our results implicate Sp140 as an important repressor of type I IFNs that is essential for resistance to bacterial infections.

scholarly journals The role of IL-5, IL-6 and IL-10 in primary and vaccine-primed immune responses to infection with Friend retrovirus (Murine leukaemia virus)

2001 ◽  
Vol 82 (6) ◽  
pp. 1349-1354 ◽  
Author(s):  
Beatrice D. Strestik ◽  
Anke R. M. Olbrich ◽  
Kim J. Hasenkrug ◽  
Ulf Dittmer
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Vaccine Virus ◽  
Live Attenuated Vaccine ◽  
Leukaemia Virus ◽  
Murine Leukaemia Virus ◽  
Friend Retrovirus ◽  
Suppressive Cytokine ◽  
Deficient Mice

The defence of a host against viral infections is strongly influenced by cytokines. We investigated the role of the B-cell stimulating cytokines IL-5 and IL-6, and the immuno-suppressive cytokine IL-10, during primary and secondary immune responses in mice against infection with Friend retrovirus (FV) (Murine leukaemia virus). IL-5−/− mice were comparable to C57BL/6 wild-type mice in their ability to control acute FV infection. In contrast, IL-6−/− and IL-10−/− mice showed significantly enhanced virus loads in spleen cells. However, this impaired control of acute FV replication did not alter the long-term control over persistent FV in IL-6−/− and IL-10−/− mice. Immunization with a live attenuated vaccine virus prior to challenge protected all three types of cytokine-deficient mice from high levels of spleen virus, despite the finding that the vaccinated IL-5- and IL-6-deficient mice had significantly reduced titres of virus-neutralizing IgG class antibodies. The results indicate that IL-6 and IL-10 contribute to primary immune responses against FV, but are dispensable during persistent infection and vaccine-primed secondary responses.

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