IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells
Authors: Jennifer Palomo
Flora Reverchon
Anne-Gaelle Besnard
Bernhard Ryffel
Wanda Niedbala
Kevin N Couper
Foo Y Liew
Tovah N Shaw
Rodrigo Guabiraba
Journal: PLoS Pathogens (2015)
Discipline: MICROBIOLOGY
Keywords: Cerebral malaria; Plasmodium sp; immune response; IL-33; experimental cerebral malaria
Affiliations: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom., Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom; INRA, UMR1282, Infectiologie et Santé publique, Nouzilly, France., CNRS-UMR7355, Orleans, France and Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France., Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom., CNRS-UMR7355, Orleans, France and Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondeboasch, Republic of South Africa., Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom; School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.

Abstract:  Cerebral malaria (CM) is a complex parasitic disease caused by Plasmodium sp. Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to the development of cerebral pathology. Using the blood-stage PbA (Plasmodium berghei ANKA) model of infection, we show here that administration of the pro-Th2 cytokine, IL-33, prevents the development of experimental cerebral malaria (ECM) in C57BL/6 mice and reduces the production of inflammatory mediators IFN-γ, IL-12 and TNF-α. IL-33 drives the expansion of type-2 innate lymphoid cells (ILC2) that produce Type-2 cytokines (IL-4, IL-5 and IL-13), leading to the polarization of the anti-inflammatory M2 macrophages, which in turn expand Foxp3 regulatory T cells (Tregs). PbA-infected mice adoptively transferred with ILC2 have elevated frequency of M2 and Tregs and are protected from ECM. Importantly, IL-33-treated mice deleted of Tregs (DEREG mice) are no longer able to resist ECM. Our data therefore provide evidence that IL-33 can prevent the development of ECM by orchestrating a protective immune response via ILC2, M2 macrophages and Tregs. 

Retracted: No

PubPeer comments:
 Two images in Figure 4A appear to overlap (red boxes). *** ![file] , 
 Figure 5A appears to have issues as well. Images differ in aspect ratio and coloring, making it difficult to understand how this could simply be an error during figure assembly. *** ![file] , 
 Similar serious concerns about Figure 6A. This suggests a systemic issue. *** ![file] , 
 Thank you for alerting us to the duplicated images. While selecting the representative images for publication, the first author inserted some of the images twice (see explanation and details in his message pasted below). These mistakes did not affect the analyses or scientific conclusions of this research. However, we have contacted the journal editors and have asked to have the corrected versions of these figures published as a corrigendum. We regret these mistakes and have taken strong measures to help ensure this will not occur in the future. ttttttttDate: 10 22 2021 To Whom It May Concern: I would like to sincerely apologize for my mistakes of inserting the wrong images of the published manuscript entitles u201cAmeliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimeru2019s Diseaseu201d published in the journal, International Journal of Molecular Sciences. The detail errors are mentioned below: (i)tFigure 4A (CA3, 12-month-old, WT+TBSA) was given from wrong group (ii)tFigure 5A (WT+Vehicle) cortex image of 6-month-old animal into Figure 5A (WT+Vehicle) cortex image of 12-month-old (iii)tFigure 5A, 6-month-old CA1 image of 5xFAD+TBSA into Figure 5A, 12-month-old CA1 image of 5xFAD+TBSA (iv)tFigure 6A, CA1, 5xFAD+TBSA into Figure 6A, 12-month-old CA1 All these errors were entirely mine and none of the co-authors were involved in these mistakes. Thank you very much for informing us about these mistakes. Sincerely, Panchanan Maiti, Ph.D. ![file] ![file] ![file] , 
 #4 Again, Dr. Dunbar, I am concerned that the explanation of what *might have* occurred does not necessarily explain what *did* occur. Aside from the concerning recordkeeping challenges demonstrated by these types of errors, in some of these cases, the original data appears to have been modified. The explanation provided to the journal does not seem to mention this at all. For example: the aspect ratio differs on some of the overlapping images (yellow boxes in #2, blue boxes in #3). If this were merely an error of mislabeling misfiling or merely selecting the wrong image during figure assembly, the aspect ratio would be expected to be identical. What assembly process would explain someone changing the aspect ratio of the images without concern about the scale bars? Lastly, while I appreciate the swiftness with which you have responded to these concerns, I do recommend that you perhaps review all of the data of this paper (including the underlying statistics) as it is possible that I have not identified all of the potential issues. For example, I just now noted another overlapping image - with different coloring - in Figure 4 (see green boxes). How does one explain why the colors are different in the overlapping regions? *** ![file] , 
 We agree with your comments and, as you have suggested, we are conducting a careful investigation of this, along with a thorough review of all the data in this study and will ask the journal editor to take appropriate measures based on these findings and will keep you posted. , 
 Could the authors comment on the apparent reuse of control tissue across two papers? The other paper is discussed here: https: pubpeer.com publications C9C2A37579D57D09291F2F990A25C3 *** ![file] ,