Role of Pneumocystis jirovecii infection in chronic obstructive pulmonary disease progression in an immunosuppressed rat Pneumocystis pneumonia model

Xue, Ting; Chen, An

doi:10.3892/etm.2020.8545

Cited by 4 publications

(5 citation statements)

References 40 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increment of inflammation and emphysema lesions is similar with previous reports described in COPD patients, where Pneumocystis colonization increases the severity of COPD disease in HIV and non-HIV patients [34,42], supporting the hypothesis that Pneumocystis is a co-factor in chronic inflammatory lung diseases [37]. Interestingly, a recent work documented the role of Pneumocystis in the development of COPD disease in immunosuppressed animals [43], indicating a novel function of this fungus in the origin of the COPD disease. The inflammation is a hallmark in COPD that leads to mucus hypersecretion, fibrosis and airway collapse due pulmonary emphysema that is associated to the severity of the disease [2].…”

Section: Discussionsupporting

confidence: 88%

Pneumocystis Exacerbates Inflammation and Mucus Hypersecretion in a Murine, Elastase-Induced-COPD Model

Rojas

Ponce

Bustos

et al. 2023

JoF

View full text Add to dashboard Cite

Inflammation and mucus hypersecretion are frequent pathology features of chronic respiratory diseases such as asthma and COPD. Selected bacteria, viruses and fungi may synergize as co-factors in aggravating disease by activating pathways that are able to induce airway pathology. Pneumocystis infection induces inflammation and mucus hypersecretion in immune competent and compromised humans and animals. This fungus is a frequent colonizer in patients with COPD. Therefore, it becomes essential to identify whether it has a role in aggravating COPD severity. This work used an elastase-induced COPD model to evaluate the role of Pneumocystis in the exacerbation of pathology, including COPD-like lung lesions, inflammation and mucus hypersecretion. Animals infected with Pneumocystis developed increased histology features of COPD, inflammatory cuffs around airways and lung vasculature plus mucus hypersecretion. Pneumocystis induced a synergic increment in levels of inflammation markers (Cxcl2, IL6, IL8 and IL10) and mucins (Muc5ac/Muc5b). Levels of STAT6-dependent transcription factors Gata3, FoxA3 and Spdef were also synergically increased in Pneumocystis infected animals and elastase-induced COPD, while the levels of the mucous cell-hyperplasia transcription factor FoxA2 were decreased compared to the other groups. Results document that Pneumocystis is a co-factor for disease severity in this elastase-induced-COPD model and highlight the relevance of STAT6 pathway in Pneumocystis pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 88%

Pneumocystis Exacerbates Inflammation and Mucus Hypersecretion in a Murine, Elastase-Induced-COPD Model

Rojas

Ponce

Bustos

et al. 2023

JoF

View full text Add to dashboard Cite

show abstract

“…These results support the idea that this fungus may be a new element that triggers pathological processes in chronic respiratory diseases, leading to an increment of the severity of the symptoms. Moreover, the role of Pneumocystis has been proposed as a key factor in the first steps of the development of COPD using immunosuppressed animals [ 41 ]. In addition, studies of human COPD patients infected with Pneumocystis jirovecii (the causative agent of human Pneumocystis infection) showed that the detection of this fungus correlates with higher pro-inflammatory cytokines levels, such as TNFα, IL6, and IL8 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Role of the Fungus Pneumocystis in IL1β Pathway Activation and Airways Collagen Deposition in Elastase-Induced COPD Animals

Coronado,

Herrada,

Rojas

2024

IJMS

View full text Add to dashboard Cite

Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus Pneumocystis, which is linked to severe COPD in human patients. Recent evidence has demonstrated that Pneumocystis significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by Pneumocystis infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1β pro-inflammatory pathway during Pneumocystis infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with Pneumocystis exhibited elevated inflammation levels, including a synergistic increase in IL-1β and Cox-2. Furthermore, protein levels of the IL-1β-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with Pneumocystis, while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with Pneumocystis compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with Pneumocystis compared with the other experimental animal groups and correlated with the increase of Tgfβ1 mRNA levels. These findings emphasize the role of Pneumocystis as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.

show abstract

“…Infected BALF EVs also include proteins involved in stress response and immune system processes, such as heat shock proteins. Heat shock proteins have been shown to be upregulated in A549 lung epithelial cells treated with P. carinii , in the lungs of Pneumocystis infection in rats, and in animal models of lung injury ( 37 – 39 ). The specific host-pathogen interactions of these host vesicles and their cargo with P. carinii and P. murina are currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from Pneumocystis carinii -infected rats impair fungal viability but are dispensable for macrophage functions

Sayson,

Ashbaugh,

Cushion

2024

Microbiol Spectr

View full text Add to dashboard Cite

Pneumocystis spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable in vitro culture system poses challenges in understanding their metabolism, and the acquisition of essential nutrients from host lungs remains unexplored. Transmission electron micrographs show that extracellular vesicles (EVs) are found near Pneumocystis spp. within the lung. We hypothesized that EVs transport essential nutrients to the fungi during infection. To investigate this, EVs from P. carinii - and P. murina -infected rodents were biochemically and functionally characterized. These EVs contained host proteins involved in cellular, metabolic, and immune processes as well as proteins with homologs found in other fungal EV proteomes, indicating that Pneumocystis may release EVs. Notably, EV uptake by P. carinii indicated their potential involvement in nutrient acquisition and a possibility for using engineered EVs for efficient therapeutic delivery. However, EVs added to P. carinii in vitro did not show increased growth or viability, implying that additional nutrients or factors are necessary to support their metabolic requirements. Exposure of macrophages to EVs increased proinflammatory cytokine levels but did not affect macrophages’ ability to kill or phagocytose P. carinii . These findings provide vital insights into P. carinii and host EV interactions, yet the mechanisms underlying P. carinii ’s survival in the lung remain uncertain. These studies are the first to isolate, characterize, and functionally assess EVs from Pneumocystis -infected rodents, promising to enhance our understanding of host-pathogen dynamics and therapeutic potential. IMPORTANCE Pneumocystis spp. are fungal pathogens that can cause severe pneumonia in mammals, relying heavily on the host for essential nutrients. The absence of an in vitro culture system poses challenges in understanding their metabolism, and the acquisition of vital nutrients from host lungs remains unexplored. Extracellular vesicles (EVs) are found near Pneumocystis spp., and it is hypothesized that these vesicles transport nutrients to the pathogenic fungi. Pneumocystis proteins within the EVs showed homology to other fungal EV proteomes, suggesting that Pneumocystis spp. release EVs. While EVs did not significantly enhance P. carinii growth in vitro , P. carinii displayed active uptake of these vesicles. Moreover, EVs induced proinflammatory cytokine production in macrophages without compromising their ability to combat P. carinii . These findings provide valuable insights into EV dynamics during host-pathogen interactions in Pneumocystis pneumonia. However, the precise underlying mechanisms remain uncertain. This research also raises the potential for engineered EVs in therapeutic applications.

show abstract

Role of Pneumocystis jirovecii infection in chronic obstructive pulmonary disease progression in an immunosuppressed rat Pneumocystis pneumonia model

Cited by 4 publications

References 40 publications

Pneumocystis Exacerbates Inflammation and Mucus Hypersecretion in a Murine, Elastase-Induced-COPD Model

Pneumocystis Exacerbates Inflammation and Mucus Hypersecretion in a Murine, Elastase-Induced-COPD Model

Role of the Fungus Pneumocystis in IL1β Pathway Activation and Airways Collagen Deposition in Elastase-Induced COPD Animals

Extracellular vesicles from Pneumocystis carinii -infected rats impair fungal viability but are dispensable for macrophage functions

Contact Info

Product

Resources

About