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Ignacio Caballero

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**Summary of Research Activity** I graduated in Veterinary Medicine in 2003 and joined the Animal Reproduction research group (E0A1-03) from the University of Murcia as a PhD student (2003-2007). The main goal of my research during my **PhD studies** was to improve the outcome of sperm cryopreservation and flow cytometric sex-sorting (that allows choosing the sex of the offspring) in porcine using seminal plasma and its proteins. I obtained my **first postdoctoral appointment** at Dr Piedrahita’s lab in North Carolina State University to develop transgenic pigs for animal and human medicine research. The main objective of the project was the development of “humanized” organs in the pig for “reverse” xenotransplantation. To achieve this goal the project was divided in 2 sub-objectives: 1) Development of a transgenic pig with a “humanized” immune system: I developed a number of transgenic pigs where the RAG2 (specific for B and T cells) and the NKp46 promoter (specific for NK cells) drove the expression of diphtheria toxin A in order to ablate the pig immune system. 2) Establishing a fetal injection protocol: I developed a pCAG-lacZfloxed-DTA transgenic pig. Pig foetuses were injected at 35 days of gestation with lacZ-positive bone marrow stem cells and lacZ-positive cells were detected in 2 month old pigs indicating that transgenic cells were able to engraft in the bone marrow and generate lacZ-positive hematopoietic cells. This transgenic pig lines are currently being used for engraftment of human hematopoietic stem cells.. In 2011, **I obtained a Marie Curie IIF (January 2011-January 2013) at the University of Sheffield, UK**. The project I was involved was “Regulation of innate immunity in the female reproductive tract”. Implantation of the embryo in the uterus is considered to be one of the most complex and critical steps during pregnancy. Sub-clinical infections in the female reproductive tract (FRT) contribute to implantation failure. Toll like receptors (TLRs), have been shown to have a key role in the induction of immune and inflammatory responses in mammals by activating both the nuclear factor kB transcription factor (NF-κB) and AP-1 transcription factors. TLRs have a cyclical expression during the menstrual cycle in the human endometrium. TLR expression also changes in oviductal and endometrial cell lines in response to sex hormones. In this project, we aimed to systemically investigate the effect of the embryo and sex hormones on the expression and function of TLR5 at population level and single cell level using live imaging confocal microscopy. Our results showed that: 1) the presence of the embryo is able to modulate TLR5 response by increasing NF-κB activity. Also, abnormal levels of NF-κB activity lead to implantation failure. 2) Single cell live imaging allowed us to determine for the first time dynamics of TLR5-mediated NF-κB pulsatile signalling. Moreover, we also showed that estradiol effect on NF-κB occurs at the transcription level in the nucleus rather than affect the translocation of NF-κB. In September 2013, I obtained a position as the **leader of the Porcine Mucosal Immunology team (**[**https://www6.val-de-loire.inra.fr/infectiologie-santepublique\_eng/Research/Bacteriology-teams/Porcine-mucosal-immunology**](https://www6.val-de-loire.inra.fr/infectiologie-santepublique_eng/Research/Bacteriology-teams/Porcine-mucosal-immunology)**) at INRA, France**. Our major interest lies in the use of the pig as a biomedical model in order to develop novel alternative therapies and immunostimulation strategies. Similarities between pigs and humans both anatomically and in the immune response make the pig a highly demanded animal model. In collaboration with the University of Munich we have established a transgenic pig line of CFTR knockout pigs that develop cystic fibrosis lung disease, a chronic inflammatory lung disease. We are also interested in new therapies that boost immunity through stimulation of Toll-like receptors. In summary, I published a total of **42 original articles** in international journals (and 1 submitted, h-index=18), 2 original articles in peer-reviewed national journals, 1 book and 9 book chapters. All the articles have been published in journals ranked in the highest positions of their area. I participated actively at **international and national conferences** with 52 poster presentations and oral communication. Most of them (28) have been published in international journals, such as Reproduction, fertility and development and Reproduction in domestic animals. I have been **invited speaker in 10 international conferences**.

Publications

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New Insights in the Interplay Between African Swine Fever Virus and Innate Immunity and Its Impact on Viral Pathogenicity

Abraham Ayanwale , Sascha Trapp , Rodrigo Guabiraba , Ignacio Caballero-Posadas , Ferdinand Roesch et al.
Frontiers in Microbiology, 2022, 13, 9 p. ⟨10.3389/fmicb.2022.958307⟩
Journal articles hal-03738722v1
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TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium

Isabelle Fleurot , Raquel López-Gálvez , Pascal Barbry , Antoine Guillon , Mustapha Si-Tahar et al.
Journal of Cystic Fibrosis, 2022, 21 (2), pp.e117-e121. ⟨10.1016/j.jcf.2021.08.002⟩
Journal articles hal-03556846v1
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Airway administration of flagellin regulates the inflammatory response to Pseudomonas aeruginosa

Raquel López-Gálvez , Isabelle Fleurot , Pablo Chamero , Sascha Trapp , Olivier Michel et al.
American Journal of Respiratory Cell and Molecular Biology, 2021, 65 (4), pp.378-389. ⟨10.1165/rcmb.2021-0125OC⟩
Journal articles hal-03258174v1
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Evidence of early increased sialylation of airway mucins and defective mucociliary clearance in CFTR-deficient piglets

Ignacio Caballero , Bélinda Ringot-Destrez , Mustapha Si-Tahar , Pascal Barbry , Antoine Guillon et al.
Journal of Cystic Fibrosis, 2021, 20 (1), pp.173-182. ⟨10.1016/j.jcf.2020.09.009⟩
Journal articles hal-02967168v1
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Where Is the Cystic Fibrosis Transmembrane Conductance Regulator?

Pascal Barbry , Brice Marcet , Ignacio Caballero
American Journal of Respiratory and Critical Care Medicine, 2021, 203 (10), pp.1214 - 1216. ⟨10.1164/rccm.202012-4434ED⟩
Journal articles hal-03264909v1
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CFTR-deficient pigs display alterations of bone microarchitecture and composition at birth

Julien Braux , Marie-Laure Jourdain , Christine Guillaume , Valérie Untereiner , Olivier Piot et al.
Journal of Cystic Fibrosis, 2020, 19 (3), pp.466-475. ⟨10.1016/j.jcf.2019.10.023⟩
Journal articles hal-02406264v1
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Intrinsic alterations in peripheral neutrophils from cystic fibrosis newborn piglets

Deborah Brea , Laura Soler , Isabelle Fleurot , Sandrine Melo , Claire Chevaleyre et al.
Journal of Cystic Fibrosis, 2020, 19 (5), pp.830-836. ⟨10.1016/j.jcf.2020.02.016⟩
Journal articles hal-03012482v1
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Tetrafunctional Block Copolymers Promote Lung Gene Transfer in Newborn Piglets

Ignacio Caballero , Mickaël Riou , Océane Hacquin , Claire Chevaleyre , Céline Barc et al.
Molecular Therapy - Nucleic Acids, 2019, 16, pp.186-193. ⟨10.1016/j.omtn.2019.02.016⟩
Journal articles inserm-02080870v1
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Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures

Sandra Ruiz Garcia , Marie Deprez , Kevin Lebrigand , Amelie Cavard , Agnès Paquet et al.
Development (Cambridge, England), 2019, 146 (20), 17p. ⟨10.1242/dev.177428⟩
Journal articles hal-02628140v1
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Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

Ignacio Caballero-Posadas , James Boyd , Carmen Alminana-Brines , Javier A. Sánchez-López , Shaghayegh Basatvat et al.
Scientific Reports, 2017, 7, 10 p. ⟨10.1038/srep40981⟩
Journal articles hal-01594679v1
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Generation of a Stable Transgenic Swine Model Expressing a Porcine Histone 2B-eGFP Fusion Protein for Cell Tracking and Chromosome Dynamics Studies

Renan B. Sper , Sehwon Koh , Xia Zhang , Sean Simpson , Bruce Collins et al.
PLoS ONE, 2017, 12 (1), 24 p. ⟨10.1371/journal.pone.0169242⟩
Journal articles hal-01607549v1
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The Pig: A Relevant Model for Evaluating the Neutrophil Serine Protease Activities during Acute Pseudomonas aeruginosa Lung Infection.

Claire Chevaleyre , Mickaël Riou , Deborah Brea , Clarisse Vandebrouck , Céline Barc et al.
PLoS ONE, 2016, 11 (12), 17 p. ⟨10.1371/journal.pone.0168577⟩
Journal articles hal-01437131v1

Interleukin-1 receptor antagonist mediates toll-like receptor 3-induced inhibition of trophoblast adhesion to endometrial cells in vitro

M. Montazeri , J.A. Sanchez-Lopez , Ignacio Caballero , N. Maslehat Lay , S. Elliott et al.
Human Reproduction, 2016, 31 (9), pp.2098-2107. ⟨10.1093/humrep/dew171⟩
Journal articles hal-02634561v1
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Computed tomography (CT) scanning facilitates early identification of neonatal cystic fibrosis piglets

Antoine Guillon , Claire Chevaleyre , Céline Barc , Mustapha Berri , Hans Adriaensen et al.
PLoS ONE, 2015, 10 (11), pp.1-12. ⟨10.1371/journal.pone.0143459⟩
Journal articles hal-01594228v1

Activation of Toll-like receptor 3 reduces actin polymerization and adhesion molecule expression in endometrial cells, a potential mechanism for viral-induced implantation failure

M. Montazeri , J.A. Sanchez-Lopez , Ignacio Caballero-Posadas , N. Maslehat Lay , S. Elliott et al.
Human Reproduction, 2015, 30 (4), pp.893-905. ⟨10.1093/humrep/deu359⟩
Journal articles hal-01171121v1
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The battle of the sexes starts in the oviduct: modulation of oviductal transcriptome by X and Y-bearing spermatozoa

Carmen Alminana , Ignacio Caballero , Paul Roy Heath , Saeedeh Maleki-Dizaji , Inmaculada Parrilla et al.
BMC Genomics, 2014, 15, pp.1-11. ⟨10.1186/1471-2164-15-293⟩
Journal articles hal-02635235v1

Local Activation of Uterine Toll-Like Receptor 2 and 2/6 Decreases Embryo Implantation and Affects Uterine Receptivity in Mice

Javier Arturo Sanchez-Lopez , Ignacio Caballero , Mehrnaz Montazeri , Nasim Maslehat , Sarah Elliott et al.
Biology of Reproduction, 2014, 90 (4), pp.1-13. ⟨10.1095/biolreprod.113.115253⟩
Journal articles hal-02637664v1
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Human Trophoblast Cells Modulate Endometrial Cells Nuclear Factor kappa B Response to Flagellin In Vitro

Ignacio Caballero , Sumiah Al Ghareeb , Shaghayegh Basatvat , Javier A. Sánchez-López , Mehrnaz Montazeri et al.
PLoS ONE, 2013, 8 (1), pp.1-10. ⟨10.1371/journal.pone.0039441⟩
Journal articles hal-02646437v1

The Effect of Glycerol Concentrations on the Post-thaw In Vitro Characteristics of Cryopreserved Sex-sorted Boar Spermatozoa

I. Parrilla , D. del Olmo , Ignacio Caballero , T. Tarantini , C. Cuello et al.
Reproduction in Domestic Animals, 2012, 47 (6), pp.965 - 974. ⟨10.1111/j.1439-0531.2012.02000.x⟩
Journal articles hal-02647199v1

Seminal Plasma Proteins as Modulators of the Sperm Function and Their Application in Sperm Biotechnologies

Ignacio Caballero , I. Parrilla , Carmen Alminana , D. del Olmo , J. Roca et al.
Reproduction in Domestic Animals, 2012, 47 (Suppl.3), pp.12-21. ⟨10.1111/j.1439-0531.2012.02028.x⟩
Journal articles hal-02649909v1

Influence of storage time on functional capacity of flow cytometrically sex-sorted boar spermatozoa

Ignacio Caballero-Posadas , Inmaculada Parrilla , Juan Vazquez , Maria Gil , Ignacio Caballero et al.
Theriogenology, 2005, 64 (1), pp.86-98. ⟨10.1016/j.theriogenology.2004.11.004⟩
Journal articles hal-03449663v1

Comparative Effects of Autologous and Homologous Seminal Plasma on the Viability of Largely Extended Boar Spermatozoa

Ignacio Caballero-Posadas , Jm Vazquez , F Centurión , H Rodríguez-Martinez , I Parrilla et al.
Reproduction in Domestic Animals, 2004, 39 (5), pp.370-375. ⟨10.1111/j.1439-0531.2004.00530.x⟩
Journal articles hal-03449115v1

A new immunosuppressed pig model to study chronic Hepatitis E infection and the genetic viral diversity

Nancy León Janampa , Ignacio Caballero-Posadas , Céline Barc , François Darrouzain , Philippe Gatault et al.
17. Congrès national de la SFM - Microbes 2022, Société Française de Microbiologie, Oct 2022, Montpellier, France
Conference papers hal-03908226v1

A new immunosuppressed pig model to study chronic Hepatitis E infection and its impact on host innate immune responses

Julien Marlet , Nancy León Janampa , Ignacio Caballero-Posadas , Céline Barc , François Darrouzain et al.
Journées d'Animation Scientifique de la FéRI 2022 - FéRi Scientific Days 2022, Fédération de Recherche en Infectiologie (FéRI), Centre Val de Loire, Jul 2022, Joué-Lès-Tours, France
Conference papers hal-03735443v1

Faecal gut microbiota composition determines susceptibility to Salmonella Enteritidis primo-colonization

Florent Kempf , Pierrette Menanteau , Ivan Rychlik , Rosanna Drumo , Ignacio Caballero et al.
OneHealth EJP Annual Scientific meeting 2020 - virtual, May 2020, virtual, France
Conference papers hal-03186758v1

Novel approaches boosting innate immunity against Pseudomonas aeruginosa

Isabelle Fleurot , Mickael Riou , Claire Chevaleyre , Sandrine Melo , Michel Olivier et al.
15. Congrès National de la Société Française de Microbiologie (SFM), Société Française de Microbiologie (SFM). FRA., Sep 2019, Paris, France. pp.436
Conference papers hal-02736599v1

The cystic fibrosis pig model : advantages and disadvantages

Ignacio Caballero-Posadas
Journée thématique Biotechnocentre « Modèles animaux et leurs alternatives: quel avenir ? », Jun 2016, Joué-les-Tours, France
Conference papers hal-02792567v1

Closing remarks

Ignacio Caballero
International Conference on Cystic fibrosis: contribution of animal models to therapeutic development, Nov 2015, Tours, France
Conference papers hal-02792244v1

Neutrophils in cystic fibrosis. Are they intrinsically defective?

Deborah Brea , Laura Soler Vasco , Antoine Guillon , Claire C. Chevaleyre , Celine Barc et al.
Journées d'Animation Scientifique de la Fédération de Recherche d'Infectiologie (FéRI), Oct 2015, Orléans, France. 2 p
Conference papers hal-02799967v1

The European CF pig model: ups, downs and perspectives

Ignacio Caballero
International Conference on Cystic fibrosis: contribution of animal models to therapeutic development, Nov 2015, Tours, France
Conference papers hal-02792552v1

Développement d'un modèle d'infection respiratoire aiguë à Pseudomonas aeruginosa chez le porc

Mickaël Riou , Claire C. Chevaleyre , Deborah Brea , Celine Barc , Clarisse Vandebrouck et al.
34. Réunion Interdisciplinaire de Chimiothérapie Anti-Infectieuse (RICAI), Nov 2014, Paris, France
Conference papers hal-02799765v1

Contribution of computed tomography (CT) scan to extend the lifespan of a porcine CFTR - / - model

Ignacio Caballero , Antoine Guillon , Celine Barc , El Mostafa Berri , Claire C. Chevaleyre et al.
8. European CF Young Investigator Meeting, Feb 2014, Paris, France. 19 Diapositives
Conference papers hal-02793962v1
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Modeling Hepatitis E infection in immunocompromised patients using a new pig model

Nancy León Janampa , Céline Barc , François Darrouzain , Philippe Gatault , Mickaël Riou et al.
17. International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD), Jun 2021, Taipei, Taiwan. 345
Conference poster hal-03388900v1

Flagellin pre-stimulation modulates the immune response to pathogens in pig airway epithelial cells

Isabelle Fleurot , Sandrine Melo , Michel Olivier , Claire Chevaleyre , Christophe Carnoy et al.
11. Symposium of the French Domestic Animal Immunology Network (IAD 2018), Mar 2018, Tours, France. , 56 p., 2018
Conference poster hal-02736823v1

CFTR-Deficient Pigs Have Altered Bone Microarchitecture and Elevated Closed Cortical Porosity at Birth

Frédéric Velard , M. Jourdain , Ignacio Caballero-Posadas , Nathalie Winter , Mustapha Si-Tahar et al.
International Conference of the American-Thoracic-Society (ATS 2018), May 2018, San Diego, United States. AMER THORACIC SOC, American Journal of Respiratory and Critical Care Medicine, 197, 2018
Conference poster hal-02734272v1

CFTR-KO pigs exhibit altered bone microarchitecture at birth

F. Velard , M. Jourdain , Ignacio Caballero-Posadas , Nathalie Winter , Mustapha Si-Tahar et al.
32. Annual North American Cystic Fibrosis Conference, Oct 2018, Denver, United States. WILEY, Pediatric Pulmonology, 53 (S2), 2018
Conference poster hal-02734331v1

Toll-like Receptor 9 Activation in Trophoblast-Endometrium Cross-talk

N. Maslehat Lay , J. Sanchez-Lopez , Mehrnaz Montazeri , Ignacio Caballero , S. Elliott et al.
49. Annual meeting of the Society for the Study of Reproduction SSR 2016, Jul 2016, San Diego, United States. , 2016
Conference poster hal-02799318v1

Le modèle européen de porc CF : un modèle unique pour décrypter les altérations de glycosylation des mucines pulmonaires

B. Ringot-Destrez , Ignacio Caballero , Mustapha Si-Tahar , P. Barbry , A. Guillon et al.
17. Colloque des jeunes chercheurs Vaincre la Mucoviscidose, Feb 2016, Paris, France. , 2016
Conference poster hal-02800304v1

The pig as a model to determine the origins of cystic fibrosis lung disease

Ignacio Caballero , Antoine Guillon , Celine Barc , Isabelle I. Lantier , Mustapha M. Berri et al.
COST Action BM1308 “Sharing Advances in Large Animal Models” (SALAAM), Dec 2015, Poznan, Poland. , 2015
Conference poster hal-02800785v1

The pig as a model for the study of the early immune response to Pseudomonas Aeruginosa

Mustapha M. Berri , Mickaël Riou , Celine Barc , Deborah Brea , Claire C. Chevaleyre et al.
Swine in Biomedical Research Conference, Jul 2014, Raleigh, United States. 2014
Conference poster hal-02795088v1

Development of a functional in vitro cell system to test the role of Tribbles-2 in embryo implantation

Shaghayegh Basatvat , Ignacio Caballero , Mehrnaz Montazeri , Javier Arturo Sanchez-Lopez , N. Maslehat Lay et al.
Tribbles Pseudokinases on the Crossroads of Metabolism, Cancer, Immunity and Development, Apr 2014, Budapest, Hungary. , 2015
Conference poster hal-02793491v1

Contribution of computed tomography (CT) scan to extend the lifespan of a porcine CFTR - / - model

Ignacio Caballero , Antoine Guillon , Celine Barc , El Mostafa Berri , Claire C. Chevaleyre et al.
8. European CF Young Investigator Meeting, Feb 2014, Paris, France. 2014
Conference poster hal-02798139v1

Développement d'un modèle d'infection respiratoire aiguë à Pseudomonas aeruginosa chez le porc

Mickaël Riou , Claire C. Chevaleyre , Deborah Brea , Celine Barc , Clarisse Vandebrouck et al.
3. Journées d'Animation Scientifique, Jun 2014, Parcay Meslay, France. 2014
Conference poster hal-02801096v1

Adjustments of glycerol concentration for improving the post-thaw quality of sex sorted boar spermatozoa

I. Parrilla , D. del Olmo , Ignacio Caballero , T. Tarantini , C. Cuello et al.
11. International Congress of the Spanish Association for Animal Reproduction (AERA), Jun 2012, Cordoba, Spain. , Reproduction in Domestic Animals, 47 (suppl.3), 2012
Conference poster hal-02745246v1

Post-thaw quality of boar semen frozen at low sperm concentration

I. Parrilla , D. del Olmo , Ignacio Caballero , T. Tarantini , M. A. Gil et al.
15. Annual Conference of the European Society for Domestic Animal Reproduction (ESDAR), Sep 2011, Antalya, Turkey. , Reproduction in Domestic Animals, 46 (suppl.3), 2011, ⟨10.1111/j.1439-0531.2011.01839.x⟩
Conference poster hal-02745244v1