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1. Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.

Author

Jonathan M Pitt, Simon Blankley, Krzysztof Potempa, Christine M Graham, Lucia Moreira-Teixeira, Finlay W McNab, Ashleigh Howes, Evangelos Stavropoulos, Virginia Pascual, Jacques Banchereau, Damien Chaussabel, and Anne O'Garra

Subjects
Medicine, Science
Abstract

Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response. Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection. Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFNαβ receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes. Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection. A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2. Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice. These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes.

Published
2016
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2. Innate-like and conventional T cell populations from hemodialyzed and kidney transplanted patients are equally compromised.

Author

Marine Baron, Renata Belo, Dominique Cathelin, Lucia Moreira-Teixeira, Claire Cartery, Eric Rondeau, Laurent Mesnard, and Maria Leite-de-Moraes

Subjects
Medicine, Science
Abstract

Clinicians are well aware of existing pharmacologically-induced immune deficient status in kidney-transplanted patients that will favor their susceptibility to bacterial or viral infections. Previous studies indicated that advanced Stage 4-5 Chronic Kidney Disease might also be regarded as an immune deficiency-like status as well, even though the mechanisms are not fully understood. Here, we analyzed the ex vivo frequency and the functional properties of both conventional and innate-like T (ILT) lymphocyte subsets in the peripheral blood of 35 patients on hemodialysis, 29 kidney transplanted patients and 38 healthy donors. We found that peripheral blood cell count of ILT cells, as iNKT (invariant Natural Killer T) and MAIT (mucosal-associated invariant T), were significantly decreased in hemodialyzed patients compared to healthy controls. This deficiency was also observed regarding conventional T cells, including the IL-17-producing CD4(+) Th17 cells. Pertaining to regulatory T cells, we also noticed major modifications in the global frequency of CD4(+)CD25(+)Foxp3(+) T lymphocytes, including the resting suppressive CD45RA(+)Foxp3lo and activated suppressive CD45RA-Foxp3hi T cell subpopulations. We found no significant differences between the immune status of hemodialyzed and kidney-transplanted subjects. In conclusion, we demonstrated that both ILT and conventional T cell numbers are equally impaired in hemodialyzed and kidney-transplanted patients.

Published
2014
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3. Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response.

Author

Jenny Carmona, Andrea Cruz, Lucia Moreira-Teixeira, Carole Sousa, Jeremy Sousa, Nuno S Osorio, Ana L Saraiva, Stefan Svenson, Gunilla Kallenius, Jorge Pedrosa, Fernando Rodrigues, Antonio G Castro, and Margarida Saraiva

Subjects
Medicine, Science
Abstract

Tuberculosis associates with a wide spectrum of disease outcomes. The Beijing (Bj) lineage of Mycobacterium tuberculosis (Mtb) is suggested to be more virulent than other Mtb lineages and prone to elicit non-protective immune responses. However, highly heterogeneous immune responses were reported upon infection of innate immune cells with Bj strains or stimulation with their glycolipids. Using both in vitro and in vivo mouse models of infection, we here report that the molecular mechanism for this heterogeneity may be related to distinct TLR activations. Among this Mtb lineage, we found strains that preferentially activate TLR2, and others that also activate TLR4. Recognition of Mtb strains by TLR4 resulted in a distinct cytokine profile in vitro and in vivo, with specific production of type I IFN. We also uncover a novel protective role for TLR4 activation in vivo. Thus, our findings contribute to the knowledge of the molecular basis underlying how host innate immune cells handle different Mtb strains, in particular the intricate host-pathogen interaction with strains of the Mtb Bj lineage.

Published
2013
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4. Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy

Author

Simona Balestrini, Matthias J. Koepp, Sonia Gandhi, Hannah M. Rickman, Gee Yen Shin, Catherine F. Houlihan, Jonny Anders-Cannon, Katri Silvennoinen, Fenglai Xiao, Sara Zagaglia, Kirsty Hudgell, Mariusz Ziomek, Paul Haimes, Adam Sampson, Annie Parker, J. Helen Cross, Rosemarie Pardington, Eleni Nastouli, Charles Swanton, Josemir W. Sander, Sanjay M. Sisodiya, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell, Souradeep Basu, Rupert Beale, Clare Beesley, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J. Blackman, Dominique Bonnet, Faye Bowker, Malgorzata Broncel, Claire Brooks, Michael D. Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby, Claudio Bussi, Simon Butterworth, Matthew Byott, Fiona Byrne, Richard Byrne, Simon Caidan, Joanna Campbell, Johnathan Canton, Ana Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Natalie Chandler, Qu Chen, Peter Cherepanov, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina Cobolli Gigli, Zena Collins, Sally Cottrell, Margaret Crawford, Laura Cubitt, Tom Cullup, Heledd Davies, Patrick Davis, Dara Davison, Vicky Dearing, Solene Debaisieux, Monica Diaz-Romero, Alison Dibbs, Jessica Diring, Paul C. Driscoll, Annalisa D'Avola, Christopher Earl, Amelia Edwards, Chris Ekin, Dimitrios Evangelopoulos, Rupert Faraway, Antony Fearns, Aaron Ferron, Efthymios Fidanis, Dan Fitz, James Fleming, Daniel Frampton, Bruno Frederico, Alessandra Gaiba, Anthony Gait, Steve Gamblin, Kathleen Gärtner, Liam Gaul, Helen M. Golding, Jacki Goldman, Robert Goldstone, Belen Gomez Dominguez, Hui Gong, Paul R. Grant, Maria Greco, Mariana Grobler, Anabel Guedan, Maximiliano G. Gutierrez, Fiona Hackett, Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Emine Hatipoglu, Lyn Healy, Judith Heaney, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Steve Hindmarsh, Rajnika Hirani, Joshua Hope, Elizabeth Horton, Beth Hoskins, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint R. Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz Huseynova, Ming-Shih Hwang, Rachael Instrell, Deborah Jackson, Mariam Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Nnennaya Kanu, George Kassiotis, Gavin Kelly, Louise Kiely, Anastacio King Spert Teixeira, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris, Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe, Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Hon Wing Liu, Sam Loughlin, Wei-Ting Lu, James I. MacRae, Akshay Madoo, Julie A. Marczak, Mimmi Martensson, Thomas Martinez, Bishara Marzook, John Matthews, Joachim M. Matz, Samuel McCall, Laura E. McCoy, Fiona McKay, Edel C. McNamara, Carlos M. Minutti, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie Montgomery, Catherine Moore, David Moore, Anastasia Moraiti, Lucia Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Aileen Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Caroline Oedekoven, Anne O'Garra, Jean D. O'Leary, Jessica Olsen, Olga O'Neill, Nicola O'Reilly, Paula Ordonez Suarez, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos Papayannopoulos, Stavroula M Paraskevopoulou, Namita Patel, Yogen Patel, Oana Paun, Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S. Perrault, Abigail Perrin, Roy Poh, Enzo Z. Poirier, James M. Polke, Marc Pollitt, Lucia Prieto-Godino, Alize Proust, Clinda Puvirajasinghe, Christophe Queval, Vijaya Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Laura Reed, Caetano Reis e Sousa, Kayleigh Richardson, Sophie Ridewood, Fiona Roberts, Rowenna Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Emilie Sanchez, Theo Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Jill A. Saunders, Chelsea Sawyer, Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Rajvee Shah Punatar, Maryam Shahmanesh, Joe Shaw, Mariana Silva Dos Santos, Margaux Silvestre, Matthew Singer, Daniel M. Snell, Ok-Ryul Song, Moira J. Spyer, Louisa Steel, Amy Strange, Adrienne E. Sullivan, Michele S.Y. Tan, Zoe H. Tautz-Davis, Effie Taylor, Gunes Taylor, Harriet B. Taylor, Alison Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Patrick Toolan-Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C. Tsai, James M.A. Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P. Vanloo, Selvaraju Veeriah, Subramanian Venkatesan, Karen Vousden, Andreas Wack, Claire Walder, Philip A. Walker, Yiran Wang, Sophia Ward, Catharina Wenman, Luke Williams, Matthew J. Williams, Wai Keong Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian A. Zagalak, Davide Zecchin, Rachel Zillwood, Santhakumari Carthiyaniamma, Jane DeTisi, Julie Dick, Andrea Hill, Karin Kipper, Birinder Kullar, Sarah Norris, Fergus Rugg-Gunn, Rebecca Salvatierra, Gabriel Shaya, Astrid Sloan, Priyanka Singh, James Varley, Ben Whatley, and Academic Medical Center

Subjects
Male, Pediatrics, CCC, Crick COVID Consortium, SWGC, Sir William Gowers Centre, Comorbidity, Residential Facilities, Cohort Studies, Behavioral Neuroscience, Epilepsy, 0302 clinical medicine, Case fatality rate, Infection control, 030212 general & internal medicine, Care Models, COVID-19, coronavirus disease 2019, Aged, 80 and over, Surveillance, Middle Aged, 3. Good health, Treatment Outcome, Neurology, UCLH, University College London Hospitals NHS Foundation Trust, PEG, percutaneous endoscopic gastrostomy, STE, St Elizabeth’s Centre, Female, medicine.symptom, PPE, personal protective equipment, Cohort study, Adult, medicine.medical_specialty, Isolation (health care), Clinical Neurology, Asymptomatic, Article, Young Adult, 03 medical and health sciences, medicine, Humans, YE, Young Epilepsy, Aged, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Infection Control, business.industry, SARS-CoV-2, Prevention, Vulnerable people, COVID-19, TM, The Meath, medicine.disease, Long-Term Care, CCE, Chalfont Centre for Epilepsy, United Kingdom, Long-term care, Neurology (clinical), business, 030217 neurology & neurosurgery, Contact tracing
Abstract

Highlights • We found a high asymptomatic rate in vulnerable people with epilepsy. • Enhanced surveillance allows to quickly contain outbreaks. • We report a low rate of COVID-19 morbidity and mortality in a long-term care facility. • Preventative measures allow reducing resident-to-resident and -to-caregiver transmission. • Children and young adults appear to have lower infection rates., In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March–6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth’s (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Published
2021

5. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers

Author

Catherine F Houlihan, Nina Vora, Thomas Byrne, Dan Lewer, Gavin Kelly, Judith Heaney, Sonia Gandhi, Moira J Spyer, Rupert Beale, Peter Cherepanov, David Moore, Richard Gilson, Steve Gamblin, George Kassiotis, Laura E McCoy, Charles Swanton, Andrew Hayward, Eleni Nastouli, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell, Souradeep Basu, Clare Beesley, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J Blackman, Dominique Bonnet, Faye Bowker, Malgorzata Broncel, Claire Brooks, Michael D Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby, Claudio Bussi, Simon Butterworth, Fiona Byrne, Richard Byrne, Simon Caidan, Joanna Campbell, Johnathan Canton, Ana Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Natalie Chandler, Qu Chen, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina Cobolli Gigli, Zena Collins, Sally Cottrell, Margaret Crawford, Laura Cubitt, Tom Cullup, Heledd Davies, Patrick Davis, Dara Davison, Annalisa D'Avola, Vicky Dearing, Solene Debaisieux, Monica Diaz-Romero, Alison Dibbs, Jessica Diring, Paul C Driscoll, Christopher Earl, Amelia Edwards, Chris Ekin, Dimitrios Evangelopoulos, Rupert Faraway, Antony Fearns, Aaron Ferron, Efthymios Fidanis, Dan Fitz, James Fleming, Bruno Frederico, Alessandra Gaiba, Anthony Gait, Liam Gaul, Helen M Golding, Jacki Goldman, Robert Goldstone, Belen Gomez Dominguez, Hui Gong, Paul R Grant, Maria Greco, Mariana Grobler, Anabel Guedan, Maximiliano G Gutierrez, Fiona Hackett, Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Lyn Healy, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Steve Hindmarsh, Rajnika Hirani, Joshua Hope, Elizabeth Horton, Beth Hoskins, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint R Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz Huseynova, Ming-Shih Hwang, Rachael Instrell, Deborah Jackson, Mariam Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Nnennaya Kanu, Louise Kiely, Anastacio King Spert Teixeira, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris, Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe, Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Hon-Wing Liu, Sam Loughlin, Wei-Ting Lu, James I MacRae, Akshay Madoo, Julie A Marczak, Mimmi Martensson, Thomas Martinez, Bishara Marzook, John Matthews, Joachim M Matz, Samuel McCall, Fiona McKay, Edel C McNamara, Carlos M Minutti, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie Montgomery, Catherine Moore, Anastasia Moraiti, Lucia Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Aileen Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Caroline Oedekoven, Anne O'Garra, Jean D O'Leary, Jessica Olsen, Olga O'Neill, Paula Ordonez Suarez, Nicola O'Reilly, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos Papayannopoulos, Namita Patel, Yogen Patel, Oana Paun, Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S Perrault, Abigail Perrin, Roy Poh, Enzo Z Poirier, James M Polke, Marc Pollitt, Lucia Prieto-Godino, Alize Proust, Rajvee Shah Punatar, Clinda Puvirajasinghe, Christophe Queval, Vijaya Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Laura Reed, Caetano Reis e Sousa, Kayleigh Richardson, Sophie Ridewood, Rowenna Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Theo Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Jill A Saunders, Chelsea Sawyer, Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Joe Shaw, Gee Yen Shin, Mariana Silva Dos Santos, Margaux Silvestre, Matthew Singer, Daniel M Snell, Ok-Ryul Song, Louisa Steel, Amy Strange, Adrienne E Sullivan, Michele SY Tan, Zoe H Tautz-Davis, Effie Taylor, Gunes Taylor, Harriet B Taylor, Alison Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Patrick Toolan-Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C Tsai, James MA Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P Vanloo, Selvaraju Veeriah, Subramanian Venkatesan, Karen Vousden, Andreas Wack, Claire Walder, Philip A Walker, Yiran Wang, Sophia Ward, Catharina Wenman, Luke Wiliams, Matthew J Williams, Wai Keong Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian A Zagalak, Davide Zecchin, Rachel Zillwood, Rebecca Matthews, Abigail Severn, Sajida Adam, Louise Enfield, Angela McBride, Kathleen Gärtner, Sarah Edwards, Fabiana Lorencatto, Susan Michie, Ed Manley, Maryam Shahmanesh, Hinal Lukha, Paulina Prymas, Hazel McBain, Robert Shortman, Leigh Wood, Claudia Davies, Bethany Williams, Kevin W Ng, Georgina H Cornish, Nikhil Faulkner, Andrew Riddell, Philip Hobson, Ana Agua-Doce, Kerol Bartolovic, Emma Russell, Lotte Carr, Emilie Sanchez, Daniel Frampton, Matthew Byott, Stavroula M Paraskevopoulou, Elise Crayton, Carly Meyer, Triantafylia Gkouleli, Andrea Stoltenberg, Veronica Ranieri, Tom Byrne, Fiona Roberts, and Emine Hatipoglu

Subjects
Adult, 2019-20 coronavirus outbreak, Infectious Disease Transmission, Patient-to-Professional, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Personnel, Pneumonia, Viral, Viral transmission, Antibodies, Viral, Risk Assessment, Article, Betacoronavirus, Environmental health, Occupational Exposure, Pandemic, Health care, London, Medicine, Humans, Prospective Studies, Seroconversion, Pandemics, Cross Infection, business.industry, SARS-CoV-2, COVID-19, General Medicine, Occupational exposure, business, Coronavirus Infections
Published
2020

6. Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis

Author

Lúcia Moreira-Teixeira, Philippa J. Stimpson, Evangelos Stavropoulos, Sabelo Hadebe, Probir Chakravarty, Marianna Ioannou, Iker Valle Aramburu, Eleanor Herbert, Simon L. Priestnall, Alejandro Suarez-Bonnet, Jeremy Sousa, Kaori L. Fonseca, Qian Wang, Sergo Vashakidze, Paula Rodríguez-Martínez, Cristina Vilaplana, Margarida Saraiva, Venizelos Papayannopoulos, and Anne O’Garra

Subjects
Science
Abstract

GM-CSF is involved in control over M. tuberculosis infection. Here the authors show that GM-CSF reduces type 1 interferon driven neutrophil recruitment, NETosis and bacterial growth in the lungs of infected mice, and provide evidence that this NETosis occurs in infected humans who are not responsive to antibiotic therapy.

Published
2020
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7. Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases

Author

Akul Singhania, Christine M. Graham, Leona Gabryšová, Lúcia Moreira-Teixeira, Evangelos Stavropoulos, Jonathan M. Pitt, Probir Chakravarty, Annika Warnatsch, William J. Branchett, Laura Conejero, Jing-Wen Lin, Sophia Davidson, Mark S. Wilson, Gregory Bancroft, Jean Langhorne, Eva Frickel, Abdul K. Sesay, Simon L. Priestnall, Eleanor Herbert, Marianna Ioannou, Qian Wang, Ian R. Humphreys, Jonathan Dodd, Peter J. M. Openshaw, Katrin D. Mayer-Barber, Dragana Jankovic, Alan Sher, Clare M. Lloyd, Nicole Baldwin, Damien Chaussabel, Venizelos Papayannopoulos, Andreas Wack, Jacques F. Banchereau, Virginia M. Pascual, and Anne O’Garra

Subjects
Science
Abstract

The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

Published
2019
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8. Myeloid Sirtuin 2 Expression Does Not Impact Long-Term Mycobacterium tuberculosis Control.

Author

Filipa Cardoso, Flávia Castro, Lúcia Moreira-Teixeira, Jeremy Sousa, Egídio Torrado, Ricardo Silvestre, António Gil Castro, Margarida Saraiva, and Teresa F Pais

Subjects
Medicine, Science
Abstract

Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-γ, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis.

Published
2015
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