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Analysis of institutional authors

Gallego Jimenez, AliciaAuthorArranz De Miguel, AliciaAuthorFresno Escudero, ManuelCorresponding AuthorMerino, JAuthor

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Induction of TLR4/TLR2 Interaction and Heterodimer Formation by Low Endotoxic Atypical LPS

Publicated to:Frontiers in Immunology. 12 748303- - 2022-01-24 12(), DOI: 10.3389/fimmu.2021.748303

Authors: Francisco, Sara; Billod, Jean-Marc; Merino, Javier; Punzon, Carmen; Gallego, Alicia; Arranz, Alicia; Martin-Santamaria, Sonsoles; Fresno, Manuel;

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Abstract

The Toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) complex is considered the major receptor of the innate immune system to recognize lipopolysaccharides (LPSs). However, some atypical LPSs with different lipid A and core saccharide moiety structures and compositions than the well-studied enterobacterial LPSs can induce a TLR2-dependent response in innate immune cells. Ochrobactrum intermedium, an opportunistic pathogen, presents an atypical LPS. In this study, we found that O. intermedium LPS exhibits a weak inflammatory activity compared to Escherichia coli LPS and, more importantly, is a specific TLR4/TLR2 agonist, able to signal through both receptors. Molecular docking analysis of O. intermedium LPS predicts a favorable formation of a TLR2/TLR4/MD-2 heterodimer complex, which was experimentally confirmed by fluorescence resonance energy transfer (FRET) in cells. Interestingly, the core saccharide plays an important role in this interaction. This study reveals for the first time TLR4/TLR2 heterodimerization that is induced by atypical LPS and may help to escape from recognition by the innate immune system.

Keywords

atypical-lpscytokinesinnate immunitytoll-like receptorsAccuracyActivationAnimalsAtypical-lpsCell lineCytokinesEndotoxinsHek293 cellsHumansImmunity, innateInflammationInnate immunityKappa-bLipid aLipopolysaccharideLipopolysaccharidesMacrophagesMiceMice, inbred c57blMice, knockoutMolecular docking simulationPorphyromonas-gingivalisRecognitionSpp.Tlr2 protein, humanTlr4 protein, humanToll-like receptor 2Toll-like receptor 4Toll-like receptors

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers in Immunology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 35/161, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.41. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 4.24 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 10.6 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-09, the following number of citations:

  • WoS: 12
  • Scopus: 28
  • Europe PMC: 12
  • OpenCitations: 26

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-09:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 67.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 64 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 6.35.
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/719224

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Francisco, S) .

the author responsible for correspondence tasks has been FRESNO ESCUDERO, MANUEL.