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Article ; Online: Genital Dysbiosis and Different Systemic Immune Responses Based on the Trimester of Pregnancy in SARS-CoV-2 Infection.

Campisciano, Giuseppina / Sorz, Alice / Cason, Carolina / Zanotta, Nunzia / Gionechetti, Fabrizia / Piazza, Maria / Carli, Petra / Uliana, Francesca Maria / Ballaminut, Lisa / Ricci, Giuseppe / De Seta, Francesco / Maso, Gianpaolo / Comar, Manola

International journal of molecular sciences

2024 Volume 25, Issue 8

Abstract: Respiratory infections are common in pregnancy with conflicting evidence supporting their association with neonatal congenital anomalies, especially during the first trimester. We profiled cytokine and chemokine systemic responses in 242 pregnant women ... ...

Abstract	Respiratory infections are common in pregnancy with conflicting evidence supporting their association with neonatal congenital anomalies, especially during the first trimester. We profiled cytokine and chemokine systemic responses in 242 pregnant women and their newborns after SARS-CoV-2 infection, acquired in different trimesters. Also, we tested transplacental IgG passage and maternal vaginal-rectal microbiomes. IgG transplacental passage was evident, especially with infection acquired in the first trimester. G-CSF concentration-involved in immune cell recruitment-decreased in infected women compared to uninfected ones: a beneficial event for the reduction of inflammation but detrimental to ability to fight infections at birth. The later the infection was acquired, the higher the systemic concentration of IL-8, IP-10, and MCP-1, associated with COVID-19 disease severity. All infected women showed dysbiosis of vaginal and rectal microbiomes, compared to uninfected ones. Two newborns tested positive for SARS-CoV-2 within the first 48 h of life. Notably, their mothers had acute infection at delivery. Although respiratory infections in pregnancy are reported to affect babies' health, with SARS-CoV-2 acquired early during gestation this risk seems low because of the maternal immune response. The observed vaginal and rectal dysbiosis could be relevant for neonatal microbiome establishment, although in our series immediate neonatal outcomes were reassuring.
MeSH term(s)	Humans ; Female ; Pregnancy ; COVID-19/immunology ; Dysbiosis/immunology ; Dysbiosis/microbiology ; Adult ; SARS-CoV-2/immunology ; Pregnancy Complications, Infectious/immunology ; Pregnancy Complications, Infectious/microbiology ; Pregnancy Complications, Infectious/virology ; Vagina/microbiology ; Vagina/immunology ; Vagina/virology ; Infant, Newborn ; Cytokines/metabolism ; Pregnancy Trimesters/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Microbiota/immunology
Chemical Substances	Cytokines ; Immunoglobulin G
Language	English
Publishing date	2024-04-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25084298
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Article ; Online: A comparison between different anti-retroviral therapy regimes on soluble inflammation markers: a pilot study.

Maritati, Martina / Alessandro, Trentini / Zanotta, Nunzia / Comar, Manola / Bellini, Tiziana / Sighinolfi, Laura / Contini, Carlo

AIDS research and therapy

2020 Volume 17, Issue 1, Page(s) 61

Abstract: Background: Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and ... ...

Abstract	Background: Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and immune activation. The use of certain antiretroviral drugs can contribute to this process. Methods: We investigated 26 potential biomarkers in serum samples from HIV-1 infected patients virologically suppressed under ART. The main objective of our study was to evaluate if virological suppression achieved with a triple drug regimen containing tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC) as backbone, could correlate with a better immunological and inflammatory profile in relation to the third class of antiretroviral drug administered. The eligible patients were then divided into 3 groups in relation to the third drug associated with TDF/FTC: nucleoside reverse transcriptase inhibitors (NNRTI) (Group 1, n = 16), protease inhibitors (PI) (Group 2, n = 17) and integrase inhibitors (INI) (Group 3, n = 16). Results: Inflammatory cytokines and chemokines were more represented in Group 2 than in Group 3 (IL-1Ra, p = 0.013; IL-12p70 p = 0.039; TNF-α p = 0.041; IL-8, p = 0.027; MIP1 β, p = 0.033). Eotaxin showed lower levels in Group 1 compared to Group 2 (p = 0.010), while IP-10 was significantly lower in Group 1 compared to both Group 2 and Group 3 (p = 0.003 and p = 0.007, respectively). Conclusions: Our results seem to discourage the administration of PI as a third drug in a virologically effective antiretroviral regimen, as its use is linked to the detection of higher levels of pro-inflammatory mediators in comparison with INI and NNRTI.
MeSH term(s)	Anti-HIV Agents/therapeutic use ; Biomarkers ; HIV Infections/drug therapy ; Humans ; Inflammation/drug therapy ; Pilot Projects
Chemical Substances	Anti-HIV Agents ; Biomarkers
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article
ISSN	1742-6405
ISSN (online)	1742-6405
DOI	10.1186/s12981-020-00316-w
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Article ; Online: The Bacterial DNA Profiling of Chorionic Villi and Amniotic Fluids Reveals Overlaps with Maternal Oral, Vaginal, and Gut Microbiomes.

Campisciano, Giuseppina / Zanotta, Nunzia / Quadrifoglio, Mariachiara / Careri, Annalisa / Torresani, Alessandra / Cason, Carolina / De Seta, Francesco / Ricci, Giuseppe / Comar, Manola / Stampalija, Tamara

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic ... ...

Abstract	The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic fluids (AF) in relation to maternal saliva, rectum, and vagina and the soluble cytokines cascade in the vagina, CV and AF. In our series, 12/37 (32%) AF and 10/23 (44%) CV tested positive for bacterial DNA. CV and AF harbored bacterial DNA of Streptococcus and Lactobacillus, overlapping that of the matched oral and vaginal niches, which showed a dysbiotic microbiome. In these pregnant women, the immune profiling revealed an immune hyporesponsiveness in the vagina and a high intraamniotic concentration of inflammatory cytokines. To understand the eventual role of bacterial colonization of the CV and AF and the associated immune response in the pregnancy outcome, further appropriate studies are needed. In this context, further studies should highlight if the hematogenous route could justify the spread of bacterial DNA from the oral microbiome to the placenta and if vaginal dysbiosis could favor the likelihood of identifying CV and AF positive for bacterial DNA.
MeSH term(s)	Pregnancy ; Female ; Humans ; Amniotic Fluid ; Chorionic Villi ; Gastrointestinal Microbiome ; DNA, Bacterial/genetics ; DNA Fingerprinting ; Bacteria/genetics ; Vagina/microbiology ; Cytokines/genetics
Chemical Substances	DNA, Bacterial ; Cytokines
Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032873
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Article ; Online: SARS-CoV-2 Infection and Inflammatory Response in a Twin Pregnancy.

Trombetta, Andrea / Comar, Manola / Tommasini, Alberto / Canton, Melania / Campisciano, Giuseppina / Zanotta, Nunzia / Cason, Carolina / Maso, Gianpaolo / Risso, Francesco Maria

International journal of environmental research and public health

2021 Volume 18, Issue 6

Abstract: There is growing literature about the SARS-CoV-2 pathogenetic effects exerted during pregnancy and whether vertical transmission or premature birth is possible. It is not well known whether changes in the immune system of pregnant women may lead to a ... ...

Abstract	There is growing literature about the SARS-CoV-2 pathogenetic effects exerted during pregnancy and whether vertical transmission or premature birth is possible. It is not well known whether changes in the immune system of pregnant women may lead to a marked susceptibility to infectious processes and the risk of adverse maternal and neonatal complications such as preterm birth, spontaneous abortion, hospitalization in an intensive care unit, transmission to the fetus or newborns, and fetal mortality are poorly understood. Along with this ongoing debate, it is not well defined whether, during pregnancy, the role of host susceptibility in producing a specific inflammatory response to SARS-CoV-2 may represent distinctive markers of risk of vertical transmission. Furthermore, SARS-CoV-2 impact on the vaginal microbiome has not yet been described, despite mounting evidence on its possible effect on the gastrointestinal microbiome and its influence on infectious diseases and preterm labor. This report describes the impact of SARS-CoV-2 on a twin pregnancy diagnosed with infection at the third trimester of gestation including tissue infections, inflammatory response, antibody production, cytokine concentration, and vaginal microbiome composition. We identified a pattern of cytokines including IL1-Ra, IL-9 G-CSF, IL-12, and IL-8 differently expressed, already associated with previously infected patients. We detected a similar concentration of almost all the cytokines tested in both twins, suggesting that the SARS-CoV-2-induced cytokine storm is not substantially impaired during the placental passage. The analysis of the vaginal microbiome did not show relevant signs of dysbiosis, similar to other healthy pregnant women and twin healthy pregnancies. The aim of this report was to analyze the immunological response against SARS-CoV-2 infection and virus tissue tropism in a twin pregnancy.
MeSH term(s)	COVID-19 ; Female ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Pregnancy ; Pregnancy Complications, Infectious ; Pregnancy Outcome ; Pregnancy, Twin ; Premature Birth ; SARS-CoV-2
Language	English
Publishing date	2021-03-17
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph18063075
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Article: Vaginal Dysbiosis and Partial Bacterial Vaginosis: The Interpretation of the "Grey Zones" of Clinical Practice.

Campisciano, Giuseppina / Zanotta, Nunzia / Petix, Vincenzo / Giangreco, Manuela / Ricci, Giuseppe / Maso, Gianpaolo / Comar, Manola / De Seta, Francesco

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 2

Abstract: Bacterial vaginosis (BV) affects one-third of reproductive age women, increasing the risk of acquiring sexually transmitted infections (STIs) and posing a risk for reproductive health. The current diagnosis with Gram stain (Nugent Score) identifies a ... ...

Abstract	Bacterial vaginosis (BV) affects one-third of reproductive age women, increasing the risk of acquiring sexually transmitted infections (STIs) and posing a risk for reproductive health. The current diagnosis with Gram stain (Nugent Score) identifies a transitional stage named partial BV or intermediate microbiota, raising the problem of how to clinically handle it. We retrospectively analyzed cervicovaginal swabs from 985 immunocompetent non-pregnant symptomaticspp. women (vaginal discharge, burning, itching) by Nugent score and qPCR for BV, aerobic or fungal vaginitis, and STIs (
Language	English
Publishing date	2021-01-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11020191
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Article ; Online: Evidence of bacterial DNA presence in chorionic villi and amniotic fluid in the first and second trimester of pregnancy.

Campisciano, Giuseppina / Quadrifoglio, Mariachiara / Comar, Manola / De Seta, Francesco / Zanotta, Nunzia / Ottaviani, Chiara / Barbieri, Moira / Chiodo, Antonella / Stampalija, Tamara

Future microbiology

2021 Volume 16, Page(s) 801–810

Abstract: The sterile-womb dogma in uncomplicated pregnancy has been lively debated. Data regarding ... ...

Abstract	The sterile-womb dogma in uncomplicated pregnancy has been lively debated. Data regarding the
MeSH term(s)	Amniotic Fluid/microbiology ; Chorionic Villi/microbiology ; DNA, Bacterial/genetics ; DNA, Bacterial/isolation & purification ; Female ; Humans ; Microbiota ; Pregnancy ; Pregnancy Trimester, Second ; RNA, Ribosomal, 16S/genetics
Chemical Substances	DNA, Bacterial ; RNA, Ribosomal, 16S
Language	English
Publishing date	2021-07-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2254620-0
ISSN	1746-0921 ; 1746-0913
ISSN (online)	1746-0921
ISSN	1746-0913
DOI	10.2217/fmb-2020-0243
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Article: The Vaginal Community State Types Microbiome-Immune Network as Key Factor for Bacterial Vaginosis and Aerobic Vaginitis.

De Seta, Francesco / Campisciano, Giuseppina / Zanotta, Nunzia / Ricci, Giuseppe / Comar, Manola

Frontiers in microbiology

2019 Volume 10, Page(s) 2451

Abstract: Regarding bacterial vaginosis (BV), the relevance of the vaginal microbiota to the women's health fulfills a key role, but knowledge gaps regarding aerobic vaginitis (AV) exist. This study aims to characterize vaginal microbiome and its relationship with ...

Abstract	Regarding bacterial vaginosis (BV), the relevance of the vaginal microbiota to the women's health fulfills a key role, but knowledge gaps regarding aerobic vaginitis (AV) exist. This study aims to characterize vaginal microbiome and its relationship with the local immune mediators, providing an opportunity to define the link between vaginal commensal microorganisms and opportunistic pathogens in the relation of a given vaginal community state type (CST). A total of 90 vaginal samples from Caucasian asymptomatic women of reproductive age (18-40 years) attending the yearly examination and not reporting any vaginal complaints were retrospectively evaluated for microbiome assessment and immune factor dosage. The samples were tested by the Ion Torrent PGM and the Luminex Bio-Plex technologies for the analysis of microbiome and immune factors, respectively. In our study, the CST classification together with the local immune response profiling represented a good predictive indicator of the vaginal health, suggesting that the predominance of a specific
Language	English
Publishing date	2019-10-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2019.02451
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Article: Force-feeding malignant mesothelioma stem-cell like with exosome-delivered miR-126 induces tumour cell killing.

Monaco, Federica / De Conti, Laura / Vodret, Simone / Zanotta, Nunzia / Comar, Manola / Manzotti, Sandra / Rubini, Corrado / Graciotti, Laura / Fulgenzi, Gianluca / Bovenzi, Massimo / Baralle, Marco / Tomasetti, Marco / Santarelli, Lory

Translational oncology

2022 Volume 20, Page(s) 101400

Abstract: Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy ...

Abstract	Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy approach is proposed. MPM-derived spheroids have been treated with exosome-delivered miR-126 (exo-miR) and evaluated for their anticancer effect. The exo-miR treatment increased MPM stem-cell like stemness and inhibited cell proliferation. However, at a prolonged time, the up taken miR-126 was released by the cells themselves through exosomes; the inhibition of exosome release by an exosome release inhibitor GW4869 induced miR-126 intracellular accumulation leading to massive cell death and in vivo tumour growth arrest. Autophagy is involved in these processes; miR-126 accumulation induced a protective autophagy and the inhibition of this process by GW4869 generates a metabolic crisis that promotes necroptosis, which was associated with PARP-1 over-expression and cyt-c and AIF release. Here, for the first time, we proposed a therapy against CSCs, a heterogeneous cell population involved in cancer development and relapse.
Language	English
Publishing date	2022-03-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2443840-6
ISSN	1936-5233
ISSN	1936-5233
DOI	10.1016/j.tranon.2022.101400
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Article: Measles: An Overview of a Re-Emerging Disease in Children and Immunocompromised Patients.

Misin, Andrea / Antonello, Roberta Maria / Di Bella, Stefano / Campisciano, Giuseppina / Zanotta, Nunzia / Giacobbe, Daniele Roberto / Comar, Manola / Luzzati, Roberto

Microorganisms

2020 Volume 8, Issue 2

Abstract: Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death ... ...

Abstract	Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is caused by the ongoing reduction of vaccination coverage. This event has triggered public and scientific interest. For this reason, we reviewed the pathophysiology of measles infection, focusing on mechanisms by which the virus spreads systemically through the host organism. By reaching the lymphocytes from the airways through a "trojan horse" strategy, measles induces an immunosuppression status. H and F glycoproteins, both expressed in the envelope, ensure attachment of the virus to host cells and spreading from one cell to another by binding to several receptors, as described in detail. The severity of the disease depends both on the age and underlying conditions of patients as well as the social and health context in which epidemics spread, and is often burdened by sequelae and complications that may occur several years after infection. Particular attention was paid to special groups that are more susceptible to severe or atypical measles. An overview of microbiology, symptoms, diagnosis, prevention, and treatment completes and enriches the review.
Language	English
Publishing date	2020-02-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms8020276
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Article ; Online: In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis.

Campisciano, Giuseppina / Zanotta, Nunzia / Licastro, Danilo / De Seta, Francesco / Comar, Manola

Scientific reports

2018 Volume 8, Issue 1, Page(s) 2307

Abstract: The microbiota fulfils a key role in the training and function of the immune system, which contributes to the symbiosis between the host and complex microbial communities. In this study, we characterized the interplay between vaginal bacteria and local ... ...

Abstract	The microbiota fulfils a key role in the training and function of the immune system, which contributes to the symbiosis between the host and complex microbial communities. In this study, we characterized the interplay between vaginal bacteria and local immune mediators during dysbiosis in selected women of reproductive age who were grouped according to Nugent's criteria. The abundance of Gardnerella vaginalis and Bifidobacterium breve was increased in the intermediate dysbiotic status, while the presence of a plethora of non-resident bacteria characterized the group with overt vaginosis. In response to these increases, the anti-inflammatory IL1ra and pro-inflammatory IL2 increased, while the embryo trophic factors FGFβ and GMCSF decreased compared to the healthy milieu. A specific pattern, including IL1α, IL1β, IL8, MIG, MIP1α and RANTES, distinguished the intermediate group from the vaginosis group, while IL5 and IL13, which are secreted by Th2 cells, were significantly associated with the perturbation of the commensals Lactobacilli, Gardnerella and Ureaplasma. Summarizing, we postulate that although the dysbiotic condition triggers a pro-inflammatory process, the presence of a steady state level of Th2 may influence clinical manifestations. These results raise clinically relevant questions regarding the use of vaginal immunological markers as efficacious tools to monitor microbial alterations.
MeSH term(s)	Adult ; Biomarkers/analysis ; Cytokines/analysis ; Dysbiosis/immunology ; Dysbiosis/microbiology ; Female ; Humans ; Microbiota/immunology ; Th2 Cells/immunology ; Vagina/immunology ; Vagina/microbiology
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2018-02-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-20649-x
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