Increased mRNA expression of key cytokines among suspected cases of Pneumocystis jirovecii infection

Mohammad Y Alshahrani,Abdulaziz S Alshahrani,Mohammed Alfaifi,Ali Hakamy,Ali G Alkhathami,Irfan Ahmad,Mirza M A Beg,Mesfer Al Shahrani,Mohamed E Hamid,Ayed A Dera,Shadma Wahab

doi:10.1186/s12879-020-05729-6

Mohammad Y Alshahrani, Abdulaziz S Alshahrani + Show 9 more

Open Access

https://doi.org/10.1186/s12879-020-05729-6

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Abstract

BackgroundPneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection.MethodsThis was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR.ResultsIncreased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p< 0.0001). Higher expression of IL-4 mRNA was found to be significantly associated with weight loss (p=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p< 0.0001). Significantly increased expression of IL-10 mRNA was observed to be associated with weight loss, dyspnea, night sweats, wheezing, and different findings of chest X-ray compared to their counterparts, whereas, IL-13 mRNA was observed in cases with fever. Suspected cases of PCP confirmed positive by IFTA with higher IL-2, IL-4, and IL-10 mRNA expression compared to negative cases. RT-PCR confirmed PCP cases had significantly higher expression of IL-2, IL-4, and IL-10 as well as IL-13 mRNA compared to negative cases. Positive detected cases by GMSS showed higher IL-2, IL-10 mRNA expression, while Giemsa showed only higher IL-4 mRNA expression compared to negative cases.ConclusionConfirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients’ management.

Highlights

Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP)
An earlier study has done to check the Messenger RNA (mRNA) expression level of cytokines of Th cells among the study cases for P. jirovecii infection, and further, the diagnosis was made by several methods such as Immune-fluorescent staining (IFAT), Gomorimethanamine silver staining (GMSS), Giemsa, Toluidine blue O (TBO), and RT-PCR method to confirm the patients and to compare the diagnostic tests [19]
The present study observed more than 5 fold, 3 fold, 4 fold, 7 fold increased mRNA expression of IL-2, IL-10, IL-4, and IL13, respectively, among the cases compared to healthy control subjects

Summary

Introduction

Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. Exclusively PCP, is a substantial contributing agent for disastrous diseases [1]. P. jirovecii is the contributing cause of PCP [2]. PCP has been a potentially lethal disease in immune-compromised patients [3]. The clinical appearance of PCP cases comprising clinical and radiological variability, management response, and consequences can be diverse broadly [4]. Several appearances of evidence recommend that the foremost causative factor for morbidity and mortality of PCP patients seems to be the host inflammatory reaction to infectious organisms rather than the organism itself [5]. Type-1 immune response encompasses the generation of Th1 cells-related cytokines, arousing macrophage beginning, the genesis of cytotoxic CD4+ T cells, and the release of antibodies for opsonizing, delayed-type hypersensitivity [6, 7]

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