Pneumocystis as a Co-Factor in Pulmonary Diseases

Rabacal, Whitney; Rayens, Emily; Norris, Karen A.

doi:10.21926/obm.genet.1804057

Cited by 2 publications

(4 citation statements)

References 94 publications

(169 reference statements)

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“…Moreover, in several aspects, the presented data in this work showed that the presence of Pneumocystis in the airways worsens features of COPD. 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.…”

Section: Discussionsupporting

confidence: 88%

“…This evidence supports the hypothesis that mild infection by Pneumocystis potentiates inflammation in respiratory diseases such as COPD directly or as a co-factor [37]. However, the mechanisms underlying this role are still unknown [37]. Therefore, we aimed to determine the role of Pneumocystis in the potentiation of inflammation and mucus secretion in a COPD host.…”

Section: Introductionsupporting

confidence: 63%

“…The observation of smoke-induced COPD in a murine model where Pneumocystis synergized with smoke in inducing severe inflammation needs further study as is comparable with the type of inflammation response seen in COPD patients [36]. This evidence supports the hypothesis that mild infection by Pneumocystis potentiates inflammation in respiratory diseases such as COPD directly or as a co-factor [37]. However, the mechanisms underlying this role are still unknown [37].…”

Section: Introductionmentioning

confidence: 56%

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

Rojas

Ponce

Bustos

et al. 2023

JoF

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 56%

See 1 more Smart Citation

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

Rojas

Ponce

Bustos

et al. 2023

JoF

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“…Recently, the association between COPD and Pneumocystis infection in regard to disease severity has been demonstrated using an elastase-induced COPD rat model showing an increase in inflammation and mucus-related markers [ 35 ]. This new evidence supports the hypothesis that a mild Pneumocystis infection may amplify inflammation or other pathophysiological features, such as fibrosis in respiratory diseases like COPD, either directly or as a co-factor [ 36 ]. However, the mechanisms underlying this role remain elusive and it is necessary to explore other pathways, such as TGFβ1 or IL1β.…”

Section: Introductionsupporting

confidence: 82%

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

Coronado,

Herrada,

Rojas

2024

IJMS

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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.

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Pneumocystis as a Co-Factor in Pulmonary Diseases

Cited by 2 publications

References 94 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

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