Browsing by Author "De Sousa, Rita"
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- Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin SignalingPublication . Zhao, Yingxin; Valbuena, Gustavo; Walker, David H.; Gazi, Michal; Hidalgo, Marylin; De Sousa, Rita; Oteo, Jose Antonio; Goez, Yenny; Brasier, Allan R.Rickettsia conorii is the etiologic agent of Mediterranean spotted fever, a re-emerging infectious disease with significant mortality. This Gram-negative, obligately intracellular pathogen is transmitted via tick bites, resulting in disseminated vascular endothelial cell infection with vascular leakage. In the infected human, Rickettsia conorii infects endothelial cells, stimulating expression of cytokines and pro-coagulant factors. However, the integrated proteomic response of human endothelial cells to R. conorii infection is not known. In this study, we performed quantitative proteomic profiling of primary human umbilical vein endothelial cells (HUVECs) with established R conorii infection versus those stimulated with endotoxin (LPS) alone. We observed differential expression of 55 proteins in HUVEC whole cell lysates. Of these, we observed induction of signal transducer and activator of transcription (STAT)1, MX dynamin-like GTPase (MX1), and ISG15 ubiquitin-like modifier, indicating activation of the JAK-STAT signaling pathway occurs in R. conorii-infected HUVECs. The down-regulated proteins included those involved in the pyrimidine and arginine biosynthetic pathways. A highly specific biotinylated cross-linking enrichment protocol was performed to identify dysregulation of 11 integral plasma membrane proteins that included up-regulated expression of a sodium/potassium transporter and down-regulation of α-actin 1. Analysis of Golgi and soluble Golgi fractions identified up-regulated proteins involved in platelet-endothelial adhesion, phospholipase activity, and IFN activity. Thirty four rickettsial proteins were identified with high confidence in the Golgi, plasma membrane, or secreted protein fractions. The host proteins associated with rickettsial infections indicate activation of interferon-STAT signaling pathways; the disruption of cellular adhesion and alteration of antigen presentation pathways in response to rickettsial infections are distinct from those produced by nonspecific LPS stimulation. These patterns of differentially expressed proteins suggest mechanisms of pathogenesis as well as methods for diagnosis and monitoring Rickettsia infections.
- Fatal Case of Crimean-Congo Hemorrhagic Fever, Portugal, 2024Publication . Zé-Zé, Líbia; Nunes, Cristina; Sousa, Micaela; De Sousa, Rita; Gomes, Carla; Santos, Ana Sofia; Alexandre, Rui T.; Amaro, Fátima; Loza, Tiago; Blanco, Miriam; Alves, MJ; Tiago Loza, Miriam Blanco, Maria J AlvesWe report a fatal case of Crimean-Congo hemorrhagic fever in Portugal. An 83-year-old man, initially suspected of having Mediterranean spotted fever, was later confirmed to have Crimean-Congo hemorrhagic fever by the detection of viral genome in the patient's serum and the presence of specific IgM antibodies.
- Rickettsioses in Latin America, Caribbean, Spain and PortugalPublication . Labruna, Marcelo B.; Mattar V, Salim; Nava, Santiago; Bermudez, Sergio; Venzal, Jose M.; Dolz, Gaby; Abarca, Katia; Romero, Luis; De Sousa, Rita; Oteo, Jose; Zavala-Castro, JorgeData on genus and infectious by Rickettsia were retrospectively compiled from the critical review literature regarding all countries in Latin America, Caribbean islands, Portugal and Spain. We considered all Rickettsia records reported for human and/or animal hosts, and/or invertebrate hosts considered being the vector. In a few cases, when no direct detection of a given Rickettsia group or species was available for a given country, the serologic method was considered. A total of 13 Rickettsia species have been recorded in Latin America and the Caribbean. The species with the largest number of country confirmed records were Rickettsia felis (9 countries), R. prowazekii (7 countries), R. typhi (6 countries), R. rickettsii (6 countries), R. amblyommii (5 countries), and R. parkeri (4 countries). The rickettsial records for the Caribbean islands (West Indies) were grouped in only one geographical area. Both R. bellii, R. akari, and Candidatus ‘R. andeane’ have been recorded in only 2 countries each, whereas R. massiliae, R. rhipicephali, R.monteiroi, and R. africae have each been recorded in a single country (in this case, R. africae has been recorded in nine Caribbean Islands). For El Salvador, Honduras, and Nicaragua, no specific Rickettsia has been reported so far, but there have been serological evidence of human or/and animal infection. The following countries remain without any rickettsial records: Belize, Venezuela, Guyana, Surinam, and Paraguay. In addition, except for a few islands, many Caribbean islands remain without records. A total of 12 Rickettsia species have been reported in Spain and Portugal: R. conorii, R. helvetica, R. monacensis, R. felis, R. slovaca, R. raoultii, R. sibirica, R. aeschlimannii, R. rioja, R. massiliae, R. typhi, and R. prowazekii. Amongst these Rickettsia species reported in Spain and Portugal, only R. prowazekii, R. typhi, R. felis, and R. massiliae have also been reported in Latin America. This study summarizes the current state of art on the rickettsial distribution in Latin America, Caribbean, Spain and Portugal. The data obtained allow a better understanding on rickettsial epidemiology and distribution of vector ecology.
- SARS-CoV-2 Seroprevalence Following a Large-Scale Vaccination Campaign in Portugal: Results of the National Serological Survey, September - November 2021Publication . Kislaya, Irina; Gonçalves, Paulo; Ramalhete, Sara; Barreto, Marta; Torres, Ana Rita; Gaio, Vânia; Gómez, Verónica; Manita, Carla; Almeida Santos, João; Soeiro, Sofia; De Sousa, Rita; Melo, Aryse; Henriques, Camila; Guiomar, Raquel; Rodrigues, Ana Paula; ISNCOVID-19 Group, On Behalf ofIntroduction: Following a COVID-19 mass vaccination campaign, it is important to evaluate the population level of SARS-CoV-2 antibodies. The aim of this study was to estimate the seroprevalence rate of SARS-CoV-2 specific antibodies acquired due to infection or vaccination in the Portuguese population. Material and methods: The National Serological Survey (third wave - ISN3COVID-19) is a cross-sectional nationwide epidemiological study developed on a sample of 4545 Portuguese residents aged one year or older, between the 28th September 2021 and the 19th November 2021. The SARS-CoV-2 anti-nucleoprotein and anti-spike IgG antibody levels were determined in serum samples using Abbott Chemiluminescent Microparticle Immunoassays. Seroprevalence estimates were stratified by age group, sex, administrative region and self-reported chronic conditions. Medians and respective 95% confidence intervals were used to describe the distribution of SARS-CoV-2 specific antibodies in specific population subgroups. Results: The total seroprevalence rate of SARS-CoV-2 was 86.4% (95% CI: 85.2% to 87.6%). A higher seroprevalence rate was estimated for women (88.3%), 50 to 59 years-old (96.5%) and in those with two or more self-reported chronic conditions (90.8%). A higher IgG (anti-Spike) concentration was observed in individuals vaccinated with the booster dose (median = 1 2601.3 AU/mL; 95% CI: 4127.5 to 19 089.1). Conclusion: There was a significant increase in SARS-CoV-2 seroprevalence following the mass vaccination campaign in Portugal. It is important to continue to monitor the distribution of specific SARS-COV-2 antibody at the population level to further inform public health policies.
- Seroprevalence of SARS-CoV-2 Infection in Portugal in May-July 2020: Results of the First National Serological Survey (ISNCOVID-19)Publication . Kislaya, Irina; Gonçalves, Paulo; Barreto, Marta; De Sousa, Rita; Garcia, Ana Cristina; Matos, Rita; Guiomar, Raquel; Rodrigues, Ana Paula; ISNCOVID-19 groupIntroduction: The aim of this study was to estimate and describe the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies (immunoglobulin M and/or immunoglobulin G) in Portugal in May-July 2020. Material and methods: A cross-sectional seroepidemiological survey was developed after the peak of the first epidemic wave on a sample of 2301 Portuguese residents, aged 1 year or older. Survey sample was selected using a two-stage stratified non-probability sampling design (quota sampling). SARS-CoV-2 immunoglobulin M and immunoglobulin G antibodies were measured in serum samples by enzyme-linked immunosorbent assay. Seroprevalence estimates of immunoglobulin M and/or immunoglobulin G and 95% confidence intervals were stratified by sex, age group, health region and education. Results: Overall, seroprevalence was 2.9% (95% confidence interval: 2.0% - 4.2%). Higher prevalence rates were observed in male (4.1%, 95% confidence interval: 2.6% - 6.6%) and those with secondary education (6.4%, 95% confidence interval: 3.2% - 12.5%). Differences in seroprevalence by age group and region were not statistically significant. Discussion: The estimated seroprevalence of SARS-CoV-2 was higher than the cumulative incidence reported by the National Surveillance System but far from necessary to reach herd immunity. Conclusion: Our results support limited extent of infection by SARS-CoV-2 in the study population possibly due to early lockdown measures implemented in Portugal and support the need to continue monitoring of SARS-CoV-2 seroprevalence in order to increase our knowledge about the evolution of the epidemic and to estimate the proportion of the susceptible population over time.
- The role of Rhipicephalus sanguineus sensu lato saliva in the dissemination of Rickettsia conorii in C3H/HeJ micePublication . Milhano, N.; Saito, T.B.; Bechelli, J.; Fang, R.; Vilhena, M.; De Sousa, Rita; Walker, D.H.Animal models have been developed for the study of rickettsial pathogenesis. However, to understand what occurs during the natural route of rickettsial transmission via the tick bite, the role of tick saliva should be considered in these models. To address this, we analysed the role of tick saliva in the transmission of Rickettsia conorii (Rickettsiales: Rickettsiaceae) in a murine host by intradermally (i.d.) inoculating two groups of susceptible C3H/HeJ mice with this Rickettsia, and infesting one group with nymphal Rhipicephalus sanguineus sensu lato (Ixodida: Ixodidae) ticks. Quantification of bacterial loads and mRNA levels of interleukin-1β (IL-1β), IL-10 and NF-κB was performed in C3H/HeJ lung samples by real-time quantitative polymerase chain reaction (PCR) and real-time reverse transcriptase PCR, respectively. Lung histology was examined to evaluate the pathological manifestations of infection. No statistically significant difference in bacterial load in the lungs of mice was observed between these two groups; however, a statistically significant difference was observed in levels of IL-1β and NF-κB, both of which were higher in the group inoculated with rickettsiae but not infected with ticks. Lung histology in both groups of animals revealed infiltration of inflammatory cells. Overall, this study showed that i.d. inoculation of R. conorii caused infection in the lungs of C3H/HeJ mice and tick saliva inhibited proinflammatory effects.