Immunomodulation for the Treatment of Fungal Infections: Opportunities and Challenges

Ademe, Muluneh

doi:10.3389/fcimb.2020.00469

Cited by 24 publications

(15 citation statements)

References 88 publications

(139 reference statements)

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“…However, such therapy has not been subjected to detailed study and so is not regularly recommended. Accordingly, immune augmentation strategies such as granulocyte colony-stimulating factor (G-CSF) and interferon- γ have been implemented as adjunctive therapies to improve host response [ 123 ]. Iron chelators such as deferasirox and deferiprone have also been shown to prevent fungal growth and protect diabetic mice from developing mucormycosis.…”

Section: Adjunctive Therapiesmentioning

confidence: 99%

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies

et al. 2021

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Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.

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Section: Adjunctive Therapiesmentioning

confidence: 99%

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies

et al. 2021

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“…Disease example: COVID‐19 outcomes are found to be worse in those inflammatory arthritis patients who are on glucocorticoids than in those who are on anti‐cytokine therapy [120] . Most pathogenic fungi are intracellular infections and immunomodulating therapeutic agents that upregulate the immune response in the fight against fungal infections hold promise for enhancing the efficacy and safety of conventional antifungal therapy [121] . This is an indication that not immunosuppression but immunoregulation is the proper target to treat Th1 oriented COVID–19 patients with severe symptoms due to cytokine storm.…”

Section: Resultsmentioning

confidence: 99%

COVID–19 and Progesterone: Part 2. Unraveling High Severity, Immunity Patterns, Immunity grading, Progesterone and its potential clinical use

Shah¹

2021

Endocrine and Metabolic Science

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Severely ill COVID–19(Corona Virus Disease of 2019) patients have a hyperinflammatory condition with a high concentration of pro-inflammatory cytokines termed the cytokine storm. This milieu is reported to cause acute lung injury, oxygen deprivation, multiorgan damage, critical illness, and often death. Post SARS–CoV–2(Severe Acute Respiratory Syndrome Coronavirus 2) infection, the fight between the invading virus and the host's immune system would either terminate in recovery, with eradication of the infection and regulation of the immune system; or there would be a continuation of immune attacks even after the virus has been cleared, leading to immune dysregulation and disease. This outcome is chiefly dependent on two factors: (1) the patient's immune response, and (2) sufficiency plus efficiency of the regulator(s). Concerning the first, the present research introduces a framework based on different types of immune responses to COVID–19 along with known disease examples,and how this relatesto varying clinical outcomes and treatment needs for COVID–19 patients. About the second factor of ‘regulator(s)’, part 1 of the manuscript described in depth the regulatory role of progesterone in COVID–19.The present study investigates the two immunity patterns and the status of the regulatory hormone progesterone with respect to the two established demographic risk factors for high-severity COVID–19: male sex, and old age. The study evaluates the status of progesterone as a credible participant of immune regulationand dysregulation. It duly relates the immunity patterns to clinical outcomes and evinces indications for clinical use of progesterone in COVID–19.It proposes a clear answer to the question: why are males and old patients most likely to have critical illness due to COVID–19? The study highlights clinical domains for the use of progesterone in COVID–19. Part 2 of this research introducing the concept of immunity patterns and immunity grading. These concepts herewith provided for the clinical course of COVID–19 also applies to other hyperinflammatory conditions. Possible clinical applications of progesterone to treat critically ill COVID–19 patients will open an avenue for hormonal treatments of infections and other immune-related diseases.

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“…Regarding PCM treatment, extended periods of antifungal therapies, infection relapses, and constant medical monitoring highlight the urgency for the development of new therapeutic alternatives, mainly strategies based on the enhancing of the immune responses ( 46 , 47 ). Moreover, the research for therapeutic approaches that aim to improve the immune system of hosts suffering of impaired immune responses is a challenge that must be pursued in order to enhance the effectiveness of the available antifungal therapies ( 4 , 48 ).…”

Section: Discussionmentioning

confidence: 99%

Antibody- Based Immunotherapy Combined With Antimycotic Drug TMP- SMX to Treat Infection With Paracoccidioides brasiliensis

et al. 2021

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Monoclonal antibodies (mAbs) are promising alternatives to treat infectious diseases, especially given their potential for applications in combination therapies with antimicrobial drugs to enhance the antifungal efficacy. Protection mediated by mAbs used to treat experimental paracoccidioidomycosis (PCM) has been demonstrated previously. Our aim in the present work was to characterize a monoclonal antibody (mAbF1.4) raised against a cell wall glycoconjugate fraction of Paracoccidioides spp. and to analyze its efficacy combined with trimethoprim-sulfamethoxazole (TMP/SMX) as treatment for experimental PCM. We demonstrated that the epitope recognized by mAbF1.4 is consistent with branched glucose residues present on a cell wall β-glucan polymer. In vitro, mAbF1.4 increased the phagocytic capacity and nitric oxide concentration induced by the macrophage cell line J774.1A, and this resulted in a significant reduction in the viability of the opsonophagocytized yeasts. In vivo, we detected a significant reduction in pulmonary fungal burdens of mice treated with mAbF1.4 in association with TMP/SMX, which correlated with increased pulmonary concentrations (determined by ELISA) of IFN- γ, TNF-α, IL-10 and IL-17. In parallel, we observed a decrease in IL-4, suggesting that the treatment was associated with a mixed Th1-Th17 type immune response. Histopathology of lung segments from mice receiving the combination therapy showed a significant reduction in granulomas, which were well-defined, and improved maintenance of lung architecture. These findings demonstrate that mAbF1.4 + TMP/SMX therapy is a promising approach to combat PCM as well as decrease disease sequelae and highlights the potential benefits of immune mediators in PCM combined immunotherapy.

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Immunomodulation for the Treatment of Fungal Infections: Opportunities and Challenges

Cited by 24 publications

References 88 publications

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies

COVID–19 and Progesterone: Part 2. Unraveling High Severity, Immunity Patterns, Immunity grading, Progesterone and its potential clinical use

Antibody- Based Immunotherapy Combined With Antimycotic Drug TMP- SMX to Treat Infection With Paracoccidioides brasiliensis

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