Tissue-specific immunity for a changing world

Weisberg, Stuart P.; Ural, Basak Burcu; Farber, Donna L.

doi:10.1016/j.cell.2021.01.042

Cited by 72 publications

(46 citation statements)

References 109 publications

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“…Reproducible immune correlates of severe COVID-19 include prolonged detection of proinflammatory cytokines such as IL-6, TNFa, and IL-8, diminished type I and type III interferon, and marked lymphopenia, as well as mixed evidence for immune exhaustion and dysfunctional myeloid populations (Galani et al, 2021;Hadjadj et al, 2020;Kusnadi et al, 2021;Lucas et al, 2020;Mathew et al, 2020;Mudd et al, 2020;Schulte-Schrepping et al, 2020;Stephenson et al, 2021;Su et al, 2020;Wilk et al, 2020). Most reports have measured host responses in peripheral blood, which may only partially reflect immune status within virally targeted tissues (Ren et al, 2021;Szabo et al, 2020;Weisberg et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Ziegler

Miao

Owings

et al. 2021

Cell

254

276

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Section: Introductionmentioning

confidence: 99%

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Ziegler

Miao

Owings

et al. 2021

Cell

254

276

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“…T cells and B cells can form long-lived immunological memory after the clearance of primary viral infection to protect the host from reinfection of the same or related viruses (7). Memory lymphocytes are generally divided into circulating memory cells that patrol the body and tissue-resident memory cells that reside in the peripheral non-lymphoid tissue (7,8). Tissue-resident T (TRM) and B (BRM) cells that reside within the respiratory tract provide immediate and superior immunity against viral re-infections (9), but dysregulated lung-resident T cell responses have also been linked with chronic lung inflammation, pathology and fibrosis following CORONAVIRUS Immune signatures underlying post-acute COVID-19 lung sequelae respiratory viral infection, particularly in older hosts (10,11).…”

Section: Introductionmentioning

confidence: 99%

Immune signatures underlying post-acute COVID-19 lung sequelae

et al. 2021

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Severe COVID-19 pneumonia survivors often exhibit long-term pulmonary sequalae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional SARS-CoV-2-specific memory T and B cells were enriched at the site of infection compared to those of blood. Detailed evaluation of the lung immune compartment revealed dysregulated respiratory CD8 + T cell responses were associated with the impaired lung function following acute COVID-19. Single cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8 + T cells contributing to persistent tissue conditions following COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae following SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.

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“…Much of our knowledge of human anti-viral immunity, including innate responses, cytokines, antibodies, and T cells, is limited to blood (for a review, see Pulendran and Davis, 2020). However, blood contains a small fraction of the total immune cells throughout the body and lacks tissue-resident immune cells , including TRM (Farber, 2021;Poon and Farber, 2020;Weisberg et al, 2021b). The generation of memory T cell responses to infection and vaccination can be followed in peripheral blood (Akondy et al, 2017;Dan et al, 2021;Graham et al, 2020;Hammarlund et al, 2003;Thom et al, 2021), though studies of infection or vaccination sites have revealed distinct dynamics, functions, and immune cell compositions compared with blood (Guvenel et al, 2020;Patel et al, 2018;Szabo et al, 2021;Poon et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex

et al. 2021

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The persistence of anti-viral immunity is essential for protection and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity in the body by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We use flow cytometry, T cell receptor sequencing, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8 + T cells recognizing the ubiquitous pathogens influenza and cytomegalovirus. Our results reveal that virus specificity determines overall magnitude, tissue distribution, differentiation, and clonal repertoire of virus-specific T cells. Age and sex influence T cell differentiation and dissemination in tissues, while T cell tissue residence and functionality are highly correlated with the site. Together, our results demonstrate how the covariates of virus, tissue, age, and sex impact the anti-viral immune response, which is important for targeting, monitoring, and predicting immune responses to existing and emerging viruses.

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Tissue-specific immunity for a changing world

Cited by 72 publications

References 109 publications

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

Immune signatures underlying post-acute COVID-19 lung sequelae

Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex

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