Papers by Lucia E Alvarado-Arnez
Viruses
The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protecti... more The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4+ profile, robust T CD8+ responses, and synthesis of interferon-gamma (IFN-γ), culminating in high titers of neutralizing antibodies. Furthermore, C-type lectin domain containing 5A (CLEC5A) has been implicated in innate outcomes in other flaviviral infections. Here, we conducted a follow-up study in volunteers immunized with YF17DD, investigating the humoral response, cellular phenotypes, gene expression, and single nucleotide polymorphisms (SNPs) of IFNG and CLEC5A, to clarify the role of these factors in early response after vaccination. Activation of CLEC5A+ monocytes occurred five days after vaccination (DAV). Following, seven DAV data showed activation of CD4+ and CD8+T cells together with early positive correlations between type II IFN and genes of innate antiviral response (STAT1, STAT2, IRF7, IR...
Cell, 2021
We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities ove... more We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities
Frontiers in Tropical Diseases, 2021
Cell, 2021
We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities ove... more We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities
Frontiers in Tropical Diseases, 2021
PLoS Neglected Tropical Diseases, 2014
Mycobacterium leprae infects macrophages and Schwann cells inducing a gene expression program to ... more Mycobacterium leprae infects macrophages and Schwann cells inducing a gene expression program to facilitate its replication and progression to disease. MicroRNAs (miRNAs) are key regulators of gene expression and could be involved during the infection. To address the genetic influence of miRNAs in leprosy, we enrolled 1,098 individuals and conducted a case-control analysis in order to study four miRNAs genes containing single nucleotide polymorphism (miRSNP). We tested miRSNP-125a (rs12975333 G.T), miRSNP-223 (rs34952329 *.T), miRSNP-196a-2 (rs11614913 C.T) and miRSNP-146a (rs2910164 G.C). Amongst them, miRSNP-146a was the unique gene associated with risk to leprosy per se (GC OR = 1.44, p = 0.04; CC OR = 2.18, p = 0.0091). We replicated this finding showing that the C-allele was over-transmitted (p = 0.003) using a transmissiondisequilibrium test. A functional analysis revealed that live M. leprae (MOI 100:1) was able to induce miR-146a expression in THP-1 (p,0.05). Furthermore, pure neural leprosy biopsies expressed augmented levels of that miRNA as compared to biopsy samples from neuropathies not related with leprosy (p = 0.001). Interestingly, carriers of the risk variant (C-allele) produce higher levels of mature miR-146a in nerves (p = 0.04). From skin biopsies, although we observed augmented levels of miR-146a, we were not able to correlate it with a particular clinical form or neither host genotype. MiR-146a is known to modulate TNF levels, thus we assessed TNF expression (nerve biopsies) and released by peripheral blood mononuclear cells infected with BCG Moreau. In both cases lower TNF levels correlates with subjects carrying the risk C-allele, (p = 0.0453 and p = 0.0352; respectively), which is consistent with an immunomodulatory role of this miRNA in leprosy.
Travel Medicine and Infectious Disease, 2018
Zika virus (ZIKV) infection has emerged in the Americas as a major threat for people living in tr... more Zika virus (ZIKV) infection has emerged in the Americas as a major threat for people living in tropical and subtropical areas with Aedes aegypti and Aedes albopictus. The infection also poses a risk to travelers visiting those regions [1,2]. Up to the period 2015–2016, ZIKV caused outbreaks and epidemics in almost 50 countries and then remained as endemic in such regions where entomological and ecoepidemiological conditions were favorable [2]. Beyond the period of acute and heightened international interest, especially after being declared a Public Health Emergency by the World Health Organization [3], research still needs to address many unanswered questions about the consequences of this viral infection, particularly during pregnancy and childhood [2,4,5]. In this setting, the study of Rodriguez-Morales et al., published in Travel Medicine and Infectious Disease (TMAID) [6], is of particular importance as it reports on the clinical manifestations and outcomes of ZIKV infection in pregnant women and their newborns in a department from Colombia. As expected, these pregnant women presented particularly rash, fever and infections during all the trimesters of gestation. Microcephaly was observed in less than 3% [6], which is consistent with similar studies, but it draws special attention to the Congenital Zika Syndrome (CZS) that may include other complications and manifestations beyond the finding of a head circumference percentile below −2 SD [1]. This study also underlines the potential influence of co-infections during pregnancy, an issue recently highlighted in other reports and studies in the Americas [7–9]. Brazil and Colombia have been fore runners in research on this topic in the South American region, but more studies from other neighboring countries, especially in the Andean region, such as Bolivia [10], are urgently needed, in order to better define the impact of ZIKV among those populations. For example, in countries such as Bolivia, since its epidemiological registry started in 2016, almost 2600 suspected cases of Zika were reported spanning the epidemics period with a significant rise in 2017 [11]. Overall, 33.7% of these cases were in women aged 15–39 years old. Even though 31 microcephaly cases associated with Zika were reported, there is a lack of studies about Zika in pregnancy and its implications. A recent study revealed that ZIKV has been circulating in tropical areas (e.g. Beni, Santa Cruz de la Sierra) [10], where Aedes aegypti is endemic [12] and most of the suspected cases are located (e.g. 17.3% Beni, and 63.1% Santa Cruz de la Sierra). Consequences of those infections as well those undiagnosed, asymptomatic women and their outcomes, are many questions that studies such as those from Rodriguez-Morales et al., published in TMAID [6], raise questions regarding outcomes for other epidemiological settings such as Bolivia. Even more, a study among 814 volunteer blood donors from the cities of Santa Cruz de la Sierra, La Paz, Cochabamba, Tarija and Beni screened for IgG against ZIKV, found that 39% in Beni, 21.5% in Santa Cruz and 0.5% in Tarija were seropositive (0% for La Paz and Cochabamba) [10]. Although the epidemic is over in most countries, further studies are necessary to investigate the effects of ZIKV on pregnancy outcomes and child development. As Rodriguez-Morales et al. stated [6], given the complex ecoepidemiological scenario, microcephaly and the CZS should remain a matter of concern in endemic areas as well in pregnant women travelling to and returning from there, including Bolivia as well. Despite being a relatively low-frequency event, CZS represents a threat for childhood development, requiring additional studies and follow-up. For the near future, this may have also implications for other potential emerging arboviral diseases with possible sequelae during pregnancy and early childhood. More studies contributing to the clinical description of pregnant women with ZIKV are urgently needed in different endemic areas, including Bolivia.
PLOS ONE, 2015
Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single ... more Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the-819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the-819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal IL10 polymorphisms:-3575 T>A (rs1800890),-2849 G>A (rs6703630),-2763 C>A (rs6693899),-1082 G>A (rs1800896) and-592 C>A (rs1800872). Results from metaanalysis supported a significant susceptibility association for the-819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11-1.34) and P-value = 3x10-5 confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10-1.31, P-value = 2x10-5). Also, meta-analysis confirmed association of-592 A allele and leprosy outcome (OR = 1.24, CI = 1.03-1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r 2 = 1.0 between the-592C>A and-819C>T SNPs. We found no evidence of association for the other IL10 polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the-819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.
Current Topics and Emerging Issues in Malaria Elimination, 2021
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Frontiers in Tropical Diseases
Advances in Experimental Medicine and Biology, 2010
... Mol Immunol 34: 391399 26. Rodriguez-Perez JM, Cruz-Robles D, Hernandez-Pacheco G, Perez-Her... more ... Mol Immunol 34: 391399 26. Rodriguez-Perez JM, Cruz-Robles D, Hernandez-Pacheco G, Perez-Hernandez N, Murguia LE, Granados J, Reyes PA, Vargas-Alarcon G (2005) Tumor necrosis factor-alpha promoter polymorphism in Mexican patients with Chagas&#x27; disease. ...
Journal of Allergy and Clinical Immunology, 2011
Symptom scores in the peak season of cypress pollen dispersion were also similar between IL-31 pr... more Symptom scores in the peak season of cypress pollen dispersion were also similar between IL-31 producers and nonproducers in response to Cry j 1, cedar crude antigen, and cypress crude antigen A-C). However, QOL scores, in which a high score means a low QOL, in the peak season of cypress pollen dispersion were significantly higher in IL-31 producers in response to Cry j 1 and cypress crude antigen, but not cedar crude antigen, compared with those seen in the respective nonproducers .
PLoS Neglected Tropical Diseases, 2014
Mycobacterium leprae infects macrophages and Schwann cells inducing a gene expression program to ... more Mycobacterium leprae infects macrophages and Schwann cells inducing a gene expression program to facilitate its replication and progression to disease. MicroRNAs (miRNAs) are key regulators of gene expression and could be involved during the infection. To address the genetic influence of miRNAs in leprosy, we enrolled 1,098 individuals and conducted a case-control analysis in order to study four miRNAs genes containing single nucleotide polymorphism (miRSNP). We tested miRSNP-125a (rs12975333 G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T), miRSNP-223 (rs34952329 *&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T), miRSNP-196a-2 (rs11614913 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T) and miRSNP-146a (rs2910164 G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C). Amongst them, miRSNP-146a was the unique gene associated with risk to leprosy per se (GC OR = 1.44, p = 0.04; CC OR = 2.18, p = 0.0091). We replicated this finding showing that the C-allele was over-transmitted (p = 0.003) using a transmission-disequilibrium test. A functional analysis revealed that live M. leprae (MOI 100:1) was able to induce miR-146a expression in THP-1 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Furthermore, pure neural leprosy biopsies expressed augmented levels of that miRNA as compared to biopsy samples from neuropathies not related with leprosy (p = 0.001). Interestingly, carriers of the risk variant (C-allele) produce higher levels of mature miR-146a in nerves (p = 0.04). From skin biopsies, although we observed augmented levels of miR-146a, we were not able to correlate it with a particular clinical form or neither host genotype. MiR-146a is known to modulate TNF levels, thus we assessed TNF expression (nerve biopsies) and released by peripheral blood mononuclear cells infected with BCG Moreau. In both cases lower TNF levels correlates with subjects carrying the risk C-allele, (p = 0.0453 and p = 0.0352; respectively), which is consistent with an immunomodulatory role of this miRNA in leprosy.
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Papers by Lucia E Alvarado-Arnez