Effects of Hematopoietic Cell Transplantation on the Pulmonary Immune Response to Infection

Zinter, Matt S; Hume, Janet R.

doi:10.3389/fped.2021.634566

Cited by 11 publications

(9 citation statements)

References 62 publications

(93 reference statements)

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“…Studies on mouse models and human patients have greatly increased our knowledge of the host immune responses to A. fumigatus and have aided in the development of novel therapeutic targets to treat IPA [reviewed in references (67,68)]. Here we highlight a few advances in the field during recent years.…”

Section: Mouse Models Of Post-hct Fungal Pneumoniamentioning

confidence: 99%

Experimental Models of Infectious Pulmonary Complications Following Hematopoietic Cell Transplantation

Zhou

Moore

2021

Front. Immunol.

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Pulmonary infections remain a major cause of morbidity and mortality in hematopoietic cell transplantation (HCT) recipients. The prevalence and type of infection changes over time and is influenced by the course of immune reconstitution post-transplant. The interaction between pathogens and host immune responses is complex in HCT settings, since the conditioning regimens create periods of neutropenia and immunosuppressive drugs are often needed to prevent graft rejection and limit graft-versus-host disease (GVHD). Experimental murine models of transplantation are valuable tools for dissecting the procedure-related alterations to innate and adaptive immunity. Here we review mouse models of post-HCT infectious pulmonary complications, primarily focused on three groups of pathogens that frequently infect HCT recipients: bacteria (often P. aeruginosa), fungus (primarily Aspergillus fumigatus), and viruses (primarily herpesviruses). These mouse models have advanced our knowledge regarding how the conditioning and HCT process negatively impacts innate immunity and have provided new potential strategies of managing the infections. Studies using mouse models have also validated clinical observations suggesting that prior or occult infections are a potential etiology of noninfectious pulmonary complications post-HCT as well.

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Section: Mouse Models Of Post-hct Fungal Pneumoniamentioning

confidence: 99%

Experimental Models of Infectious Pulmonary Complications Following Hematopoietic Cell Transplantation

Zhou

Moore

2021

Front. Immunol.

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“…Some non in fec tious lung injuries are likely late sequelae from an acute infec tious pro cess, eg, BOS, linked to viral infec tions after HCT, and pro gres sion has been linked to infec tions as well. 83…”

Section: The Chang Ing Land Scape Of Lung Injury After Hct Infections...mentioning

confidence: 99%

Noninfectious lung complications of hematopoietic cell transplantation

Williams

2021

Hematology

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Noninfectious lung diseases contribute to nonrelapse mortality. They constitute a spectrum of diseases that can affect the parenchyma, airways, or vascular pulmonary components and specifically exclude cardiac and renal causes. The differential diagnoses of these entities differ as a function of time after hematopoietic cell transplantation. Specific diagnosis, prognosis, and optimal treatment remain challenging, although progress has been made in recent decades.

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“…Interestingly, following RSV infection alveolar macrophages have been shown to be the key cell type for initiating the type I interferon through a MAVS-dependent mechanism [35, 36]. While alveolar macrophages largely populate the lungs during embryogenesis and are maintained by local proliferation during homeostasis [37, 38] following conditioning for HSC transplantation alveolar macrophage can be repopulated from the donor HSC compartment [39-42]. Therefore, to specifically address the role of Mavs in alveolar macrophages, we purified Siglec F + cells from the lungs of naïve Mavs (fl/fl) or Mavs (Cd11c/Cd11c) mice and transferred 5×10 5 Siglec F + cells intratracheally into Mavs (Cd11c/Cd11c) mice one day prior to challenging with 4×10 7 conidia of the CEA10 strain (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

MAVS expression in alveolar macrophages is essential for host resistance against Aspergillus fumigatus

Wang

Cunha

Grau

et al. 2021

Preprint

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Our recent data demonstrates a critical role of the RIG-I-like receptor (RLR) family in regulating antifungal immunity against Aspergillus fumigatus in a murine model. However, the importance of this pathway in humans and the cell type(s) which utilize this innate immune receptor to detect A. fumigatus remains unresolved. Here we demonstrate that a polymorphism in human MAVS present in the donor genome was associated with the incidence of invasive pulmonary aspergillosis (IPA) in recipients of hematopoietic stem cell transplantation (HSCT). Moreover, in a separate cohort of confirmed IPA patients, polymorphisms in the IFIH1 gene alter the inflammatory response, including interferon-responsive chemokines. Returning to our murine model, we now demonstrate that CD11c+ alveolar macrophages require Mavs expression to maintain host resistance against A. fumigatus. Our data support the role of MAVS signaling in mediating antifungal immunity in both mice and human at least in part through the role of MAVS-dependent signaling in alveolar macrophages.

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Effects of Hematopoietic Cell Transplantation on the Pulmonary Immune Response to Infection

Cited by 11 publications

References 62 publications

Experimental Models of Infectious Pulmonary Complications Following Hematopoietic Cell Transplantation

Experimental Models of Infectious Pulmonary Complications Following Hematopoietic Cell Transplantation

Noninfectious lung complications of hematopoietic cell transplantation

MAVS expression in alveolar macrophages is essential for host resistance against Aspergillus fumigatus

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