News

28 June 2019

An international team of researchers led by Professor Ido Amit from the Weizmann Institute of Science, Israel with Dr Florent Ginhoux and Dr Camille Blériot from the Singapore Immunology Network (SIgN), A*STAR and Dr Zhaoyuan Liu, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), has revealed a new mechanism protecting from obesity-related metabolic disorder. They have identified a new population of immune cells called Lipid-Associated Macrophages or LAMs localized in the adipose tissue and have shown that these cells protect the organism from obesity-associated damages notably because of the expression of the gene TREM2. These findings may have important implications for the development of LAM/TREM2-targeted immunotherapies for a wide range of metabolic diseases.

Read more in: Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, Lundgren P, Bleriot C, Liu Z, Deczkowska A, Keren-Shaul H, David E Zmora N, Eldar SM, Lubezky N, Shibolet O, Hill DA, Lazar MA, Colonna M, Ginhoux F, Shapiro H, Elinav E, Amit I. Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner. Cell. 2019 Jun 27. [Epub ahead of print]

25 June 2019

In this study published in Nature Immunology, Dr. Regine Dress and Dr. Florent Ginhoux from SIgN resolve the debate about the origin and lineage affiliation of plasmacytoid dendritic cells. They discovered that plasmacytoid dendritic cells exclusively develop from IL7Rα-expressing lymphoid progenitors, rather than myeloid progenitors as previously believed, and should be considered innate lymphoid cells rather than dendritic cells. This novel knowledge of plasmacytoid dendritic cell ontogeny will enhance our understanding of the function of these cells, and their interactions with other immune cells during steady state and the many diseases they are implicated in.

Read more in: Dress RJ, Dutertre CA, Giladi A, Schlitzer A, Low I, Shadan NB, Tay A, Lum J, Kairi MFBM, Hwang YY, Becht E, Cheng Y, Chevrier M, Larbi A, Newell EW, Amit I, Chen J, Ginhoux F. Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage.Nat Immunol. 2019 Jul;20(7):852-864.

21 June 2019

Dr Amit Singhal from SIgN, in collaboration with Prof Hardy Kornfeld (UMASS, Worcester, USA) and Prof Robert Wallis (Aurum Institute, Johannesburg, SA) received an NIH U01 award (USD 2.91m) to conduct a clinical trial of “metformin as a Host-Directed Therapy for TB”. Dr Singhal was the first to propose usefulness of metformin, a diabetic drug, as an adjunct therapy for TB (https://stm.sciencemag.org/content/6/263/263ra159). Since then, number of retrospective clinical studies including his (https://erj.ersjournals.com/content/53/3/1801695.abstract), describing ~ 280,000 individuals treated with metformin for diabetes showed that metformin reduces the risk for TB infection, progression to TB disease, mortality, lung cavitation and relapse, and that it accelerates sputum conversion independent of glycemic control.

09 July 2019

Researchers from A*STAR’s Singapore Immunology Network (SIgN) in collaboration with the Pasteur Institute in France have studied the expression of immune-related genes in O’nyong nyong virus (ONNV) -infected mosquitoes. Led by Dr Guillaume Carissimo (Research Fellow from Prof Lisa Ng's Lab), the team first determined that the ideal moment to collect mRNA from the mosquitos was three days after the insects had been fed a bloodmeal containing ONNV. At this time point, the ‘battle’ between ONNV and the mosquito’s immune system is taking place in the mosquito’s midgut, which allows the team to assess which genes are expressed differently during this critical phase of first contact.

Media Mentions: Science &Technology Research News

03 July 2019

The National Research Foundation (NRF) has awarded SIgN a Shared Infrastructure Support (SIS) grant in March 2019 for five years. The grant will be used to enhance SIgN’s core capabilities in the areas of Flow Cytometry, Multiple Analysis of Proteins (MAP) and Bioinformatics, as well as develop talent to be well-versed with cutting-edge technologies and contribute to impactful scientific research. With this grant, SIgN will be even better-equipped to develop novel assays to expand its repertoire of cutting-edge technologies for higher throughput, greater quality assurance and increased scientific excellence.

Click here for Scientific News Alert.

10 June 2019

The European Asthma, Allergy and Clinical Immunology (EAACI) Congress 2019 offeres 100 scholarships to EAACI Junior Members. Dr Anand Andiappan (SIgN Fellow) was one of the recipients of the scholarship.

Dr Anand Andiappand with EAACI President at the Scholarship Award Ceremony in Lisbon Portugal on 3rd June 2019.

30 April 2019

Visualizing live cells in the brain has been a long standing challenge. In this study, the authors discovered a new probe, CDr20, which allows to track the major brain immune cells called microglia. CD20r only get fluorescent in microglia due to the presence of a protein named Ugt1a7c. The discovery of this fluorogenic probe open new doors for identifying and studying microglia in vivo, especially in the disease context, as microglia is involved in the pathophysiology of numerous brain disorders, including Alzheimer’s Disease.

Read more in: Kim B, Fukuda M, Lee JY, Su D, Sanu S, Silvin A, Khoo ATT, Kwon T, Liu X, Chi W, Liu XG, Choi S, Wan DSY, Park SJ, Kim JS, Ginhoux F, Je HS and Chang YT. Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate. Angew Chem Int Ed Engl. 2019 Apr 30. [Epub ahead of print]

29 April 2019

An international collaboration between the team led by Dr Norman Pavelka (PI, SIgN) and the team headed by Prof Judith Berman (Tel Aviv University, Israel) led to an important discovery at the crossroads of cancer and fungal infections. Using a combination of genetics and experimental evolution, the team found that Candida albicans, the most important fungal pathogen of humans, can rapidly adapt to survive in the presence of certain chemotherapeutic drugs currently used in cancer patients, such as hydroxyurea (HU). The mechanism of survival required alteration in the number of copies of specific chromosomes in the fungus’ genome, a mutation commonly referred to as aneuploidy. Interestingly, the same aneuploidy that allowed C. albicans to survive the HU treatment also conferred increased survival to an unrelated drug – the first-line antifungal drug caspofungin, which if often administered to cancer patients suffering from fungal infections. The team went on to show that mice infected by an HU-adapted strain of C. albicans carrying that particular aneuploidy were refractory to caspofungin treatment. If confirmed in the clinic, these results could have important implications for the management of cancer patients, who are at elevated risk of developing fungal infections because of the immunosuppression resulting from chemotherapy.

Read more in: Yang F, Teoh F, Tan ASM, Cao Y, Pavelka N, Berman J. Aneuploidy enables cross-adaptation to unrelated drugs. Mol Biol Evol. 2019 Apr 27. [Epub ahead of print]

26 April 2019

CHIKV outbreaks are still prevalent, with significant increase in incidences in the last decade. Given the acute and chronic disabilities caused by CHIKV infection, and the associated economic burden, effective preventive measures are urgently needed to halt CHIKV global expansion. However, there is currently no full-length live-attenuated vaccine against CHIKV. In this study, we show that mutations on key sites in CHIKV non-structural proteins could affect infectivity. Consequentially, animals endure milder disease and clear virus rapidly. Importantly, vaccination with attenuated virus induces long-lasting neutralizing antibodies against CHIKV, which protects against subsequent infections. 

Read more in: Chan YH, Teo TH, Utt A, Tan JJ, Amrun SN, Abu Bakar F, Yee WX, Becht E, Lee CY, Lee B, Rajarethinam R, Newell E, Merits A, Carissimo G, Lum FM, Ng LF. Mutating chikungunya virus non-structural protein produces potent live-attenuated vaccine candidate. EMBO Mol Med. 2019 Apr 23. [Epub ahead of print]

29 March 2019

Dr Baptiste Janela and Dr Florent Ginhoux, in collaboration with Nestlé Skin Health R&D/ GALDERMA, found that dermal cDC1 control the sustained recruitment and survival of neutrophils through VEGFα secretion in response to cutaneous bacterial infection. Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. In this study, they found that cDC1s, but not cDC2s, regulated the magnitude of the immune response to various types of bacterial infection by controlling neutrophil recruitment, survival, and functions in inflamed skin. Using single-cell mRNA sequencing, they identified a minor subset of activated EpCAM +CD59 +Ly-6D + cDC1s control neutrophil biology via the specific secretion of the cytokine vascular endothelial growth factor α (VEGF-α). Similar observations were made in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation. Such murine/human parallel comparative study at both transcriptomic and cellular levels will aid understanding of human immune response to bacterial infection and more importantly, may facilitate the development of new molecular targets for the treatment of Acne Vulgaris and others bacterial infections.

Read more in: Janela B, Patel AA, Lau MC, Goh CC, Msallam R, Kong WT, Fehlings M, Hubert S, Lum J, Simoni Y, Malleret B, Zolezzi F, Chen J, Poidinger M, Satpathy AT, Briseno C, Wohn C, Malissen B, Murphy KM, Maini AA, Vanhoutte L, Guilliams M, Vial E, Hennequin L, Newell E, Ng LG, Musette P, Yona S, Hacini-Rachinel F, Ginhoux F. A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils. Immunity. 2019 Mar 26. [Epub ahead of print]

15 March 2019

Here, using single-cell mRNA sequencing, Chakarov et al., found that two independent MRTMs populations exist across tissues with specific niche-dependent phenotype and functional programming. 

Their different roles in homeostasis, immune regulation, and fibrosis renders them attractive and separate cellular targets for the therapeutic exploitation of RTM subsets.

Chakarov S, Lim HY, Tan L, Lim SY, See P, Lum J, Zhang XM, Foo S, Nakamizo S, Duan K, Kong WT, Gentek R, Balachander A, Carbajo D, Bleriot C, Malleret B, Tam JKC, Baig S, Shabeer M, Toh SES, Schlitzer A, Larbi A, Marichal T, Malissen B, Chen J, Poidinger M, Kabashima K, Bajenoff M, Ng LG, Angeli V, Ginhoux F. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science. 2019 Mar 15;363(6432).

Click on the following links to access the paper.
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01 March 2019

Immune cells that protect us from infection might also help us see, suggests this new study, led by the group of Dr Daniel Saban in the Duke Eye Center and in collaboration with the group of Florent Ginhoux in SIgN A*STAR.

Their findings revealed that the immune system is actually needed to help nerve cells in the retina respond appropriately for vision. The research team also showed that these same exact immune cells, called microglia, also protect the retina in inherited diseases that cause blindness in mice. This work may lead to a new understanding for the causes of vision loss in such inherited retinal diseases in patients, which affects several million worldwide. Microglia are traditionally thought of in terms of protecting nerves from infection, but scientists are now appreciating that these immune cells also play key roles in supporting the function of nerves even when there is no infection present. Scientists have known for many years that immune cells are in the retina and that their numbers increase in inherited retinal diseases. This increase is also observed in in another type of retinal disease called age-related macular degeneration (AMD) that affects several million people in the U.S. alone. The precise identity of these immune cells in the disease setting was unknown as microglia are easily mistaken for another immune cell type that can come in from the blood, called monocytes. Also unclear in the field is whether these immune cells in retinal disease are part of problem, or rather are perhaps acting in some protective manner against the disease. These questions are important as immune cells accumulate next the critical layer in disease, called the retinal pigmented epithelium. Deterioration of this layer is thought to be a major cause of vision loss in AMD. This study shows that microglia, not monocytes, accumulate next to the retinal pigmented epithelium in murine model of the disease and that microglia actually protect this layer. Since scientists are focused on trying to find out why the retinal pigmented epithelium deteriorates in AMD and how it can be protected to halt disease, these new findings may offer new clues to the field. The next steps will be to understand exactly how microglia protect this layer in disease and whether this system can be used for therapeutic purposes in retinal degenerative diseases. The results of this study were published in the peer-reviewed journal Immunity in March 2019.

Read more in: O'Koren EG, Yu C, Klingeborn M, Wong AYW, Prigge CL, Mathew R, Kalnitsky J, Msallam RA, Silvin A, Kay JN, Bowes Rickman C, Arshavsky VY, Ginhoux F, Merad M, Saban DR. Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration. Immunity. 2019 Feb 26. [Epub ahead of print]

25 February 2019

Dr Florent Ginhoux in collaboration with the laboratory of Dr Sonia Garel, ENS Paris, reported in the journal “Cell” that the microbiome influences prenatal and adult microglia in a sex-specific manner. Microglia, the resident macrophages of the central nervous system, constitute the first line of defense against injury and infections and represent a novel and important cellular target to potentially alleviate and cure brain diseases. The authors found that microbiome changes have a sex- and time-specific impact on microglia: while embryonic male microglia are very sensitive to the absence of microbiome, only female microglia show significant transcriptomic changes in adulthood in the absence of microbiome. Such age-dependent sex-specific differences is crucial as sex-specific modulation of symptoms by the microbiota has been reported in models of several diseases including Parkinson’s disease or type 1 diabetes. Furthermore, irrespective of the underlying mechanisms, the identification of such distinct temporal windows for enhanced microglial alterations in response to long-term environmental challenges is relevant as epidemiological studies show that males are more susceptible to embryonic and early life challenges such as inflammation, leading to an increased risk factor for Autism Spectrum Disorders (ASD) or earlier onset of schizophrenia. Conversely, depression, auto-immune diseases and Multiple Sclerosis, which develop in adolescents or adults, show a higher occurrence rate in females. These results reveal that microglia act as time and sex-dependent responders to environmental challenges, with a potential direct influence on the etiology of the sex bias observed in pathologies associated with microglial dysfunction.

Thion MS, Low D, Silvin A, Chen J, Grisel P, Schulte-Schrepping J, Blecher R, Ulas T, Squarzoni P, Hoeffel G, Coulpier F, Siopi E, David FS, Scholz C, Shihui F, Lum J, Amoyo AA, Larbi A, Poidinger M, Buttgereit A, Lledo PM, Greter M, Chan JKY, Amit I, Beyer M, Schultze JL, Schlitzer A, Pettersson S, Ginhoux F, Garel S. Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner. Cell. 2018 Jan 25;172(3):500-516.e16.