Research square
Authors: Choi SS, van Unen V, Zhang H, Rustagi A, Alwahabi SA, Santos AJM, Chan JE, Lam B, Solis D, Mah J, Röltgen K, Trope W, Guh-Siesel A, Lin Z, Beck A, Edwards C, Mallajosyula V, Martin BA, Dunn JCY, Shrager J, Baric RA, Pinsky B, Boyd SD, Blish CA, Davis MM, Kuo CJ
Tissue-resident immunity underlies essential host defenses against pathogens, but analysis in humans has lacked model systems where epithelial infection and accompanying resident immune cell responses can be observed . Indeed, human primary epithelial organoid cultures typically omit immune cells, and human tissue resident-memory lymphocytes are conventionally assayed without an epithelial infection component, for instance from peripheral blood, or after extraction from organs. Further, the study of resident immunity in animals can be complicated by interchange between tissue and peripheral immune compartments. To study human tissue-resident infectious immune responses in isolation from secondary lymphoid organs, we generated adult human lung three-dimensional air-liquid interface (ALI) lung organoids from intact tissue fragments that co-preserve epithelial and stromal architecture alongside endogenous lung-resident immune subsets. These included T, B, NK and myeloid cells, with CD69CD103 tissue-resident and CCR7 and/or CD45RA T and conservation of T cell receptor repertoires, all corresponding to matched fresh tissue. SARS-CoV-2 vigorously infected organoid lung epithelium, alongside secondary induction of innate cytokine production that was inhibited by antiviral agents. Notably, SARS-CoV-2-infected organoids manifested adaptive virus-specific T cell activation that was specific for seropositive and/or previously infected donor individuals. This holistic non-reconstitutive organoid system demonstrates the sufficiency of lung to autonomously mount adaptive T cell memory responses without a peripheral lymphoid component, and represents an enabling method for the study of human tissue-resident immunity.
View on PubMed
CPT: pharmacometrics & systems pharmacology
Authors: Chawla A, Largajolli A, Hussain A, Kleijn H, Ait-Oudhia S, Anton J, Ananthula H, Nussbaum J, La Rosa C, Gheyas F
JAMA health forum
Authors: Maisel N, Thombley R, Overhage JM, Blake K, Sinsky CA, Adler-Milstein J
Tobacco control
Authors: Islam T, Eckel S, Liu F, Barrington-Trimis J, Harlow AF, Benowitz N, Leventhal A, McConnell R, Cho J
Research square
Authors: Branche A, Rouphael N, Diemert D, Falsey A, Losada C, Baden LR, Frey S, Whitaker J, Little S, Anderson E, Walter E, Novak R, Rupp R, Jackson L, Babu T, Kottkamp A, Luetkemeyer A, Immergluck L, Presti R, Backer M, Winokur P, Mahgoub S, Goepfert P, Fusco D, Malkin E, Bethony J, Walsh E, Graciaa D, Samaha H, Sherman A, Walsh S, Abate G, Oikonomopoulou Z, Sahly HE, Martin T, Kamidani S, Smith M, Ladner B, Porterfield L, Dunstan M, Wald A, Davis T, Atmar R, Mulligan M, Lyke K, Posavad C, Meagher M, Stephens D, Neuzil K, Abebe K, Hill H, Albert J, Telu K, Mu J, Lewis T, Giebeig L, Eaton A, Netzl A, Wilks S, Tureli S, Makhene M, Crandon S, Montefiori D, Makowski M, Smith D, Nayak S, Roberts P, Beigel J
Chest
Authors: Kolaitis NA
Cancer research
Authors: Ding YC, Song H, Adamson AW, Schmolze D, Hu D, Huntsman S, Steele L, Patrick CS, Tao S, Hernandez N, Adams CD, Fejerman L, Gardner K, Nápoles AM, Perez-Stable EJ, Weitzel JN, Bengtsson H, Huang FW, Neuhausen SL, Ziv E
Annals of translational medicine
Authors: Rashmi P, Sigdel TK, Rychkov D, Damm I, Da Silva AA, Vincenti F, Lourenco AL, Craik CS, Reiser J, Sarwal MM
JACC. Clinical electrophysiology
Authors: Myadam R, Crawford TC, Bogun FM, Gu X, Ellenbogen KA, Jasti S, Chicos AB, Roukoz H, Zimetbaum PJ, Kalbfleisch SJ, Murgatroyd FD, Steckman DA, Rosenfeld LE, Garlitski AC, Soejima K, Bhan AK, Vedantham V, Dickfeld TL, De Lurgio DB, Platonov PG, Zipse MM, Nishiuchi S, Ortman ML, Narasimhan C, Patton KK, Rosenthal DG, Mukerji SS, Hoogendoorn JC, Zeppenfeld K, Sauer WH, Kron J, Cardiac Sarcoidosis Consortium
International journal of cardiology
Authors: Lee WJ, Cheng H, Whitney BM, Nance RM, Britton SR, Jordahl K, Lindstrom S, Ruderman SA, Kitahata MM, Saag MS, Willig AL, Burkholder G, Eron JJ, Kovacic JC, Björkegren JLM, Mathews WC, Cachay E, Feinstein MJ, Budoff M, Hunt PW, Moore RD, Keruly J, McCaul ME, Chander G, Webel A, Mayer KH, Delaney JA, Crane PK, Martinez C, Crane HM, Hao K, Peter I
