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. 2022 Mar 1;14(1):e2022022.
doi: 10.4084/MJHID.2022.022. eCollection 2022.

T-lymphocytes Expression of Toll-like Receptors 2 and 4 in Acute Myeloid Leukemia Patients with Invasive Fungal Infections

Muhamad R Abdel Hammed  1 , Sherein G Elgendy  2 , Mohamed A El-Mokhtar  2 , Douaa Sayed  3 , Samar M Mansour  3 , Abeer M Darwish  3
Affiliations

T-lymphocytes Expression of Toll-like Receptors 2 and 4 in Acute Myeloid Leukemia Patients with Invasive Fungal Infections

Muhamad R Abdel Hammed et al. Mediterr J Hematol Infect Dis. .

Abstract

Background: Invasive fungal infections (IFIs) are important cause of mortality in acute myeloid leukemia (AML) patients on treatment with intensive induction chemotherapy. Toll-like receptors, mainly Toll-like receptors 2 and 4 (TLR2 and TLR4), play a considerable role in the host defense against microorganisms. The involvement of TLR signaling in modulation of innate immune response is extensively discussed, but the TLR expressions profiling on adaptive immune cells are not specified. Also, the expressions of TLRs and their association with the occurrence of IFIs in patients with AML are not studied. So, the novel aim of this study was to investigate the associations between the T-lymphocyte expression of TLR2 and TLR4 and the occurrence of IFIs in AML patients treated with intensive induction chemotherapy.

Materials and methods: One hundred twenty two newly diagnosed AML patients were evaluated. The laboratory diagnostic techniques for IFIs include culture, microscopic examination, histopathology, galactomannan assay and PCR. The expressions of TLR2 and TLR4 were analyzed by flow cytometry. The Control group included 20 age and sex-matched individuals.

Results: There was a significant increase in the expression of TLR4 in AML patients with IFI compared to healthy controls (p = 0.001). TLR2 and TLR4 expressions increased significantly in AML patients with mixed fungal and bacterial infection compared to healthy controls (p= 0.002 and p=0.001, respectively).

Conclusion: TLRs expressions could be important biological markers for the occurrence of IFI in non-M3 AML patients after intensive induction chemotherapy.

Keywords: Acute Myeloid Leukemia; Invasive Fungal Infection; TLR2; TLR4.

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Conflict of interest statement

Competing interests: The authors declare no conflict of Interest.

Figures

Figure 1
Figure 1. Representative gating strategy used to detect the TLR2+ and TLR4+ T cells
Blood samples were stained with PerCP-conjugated anti-HLA-DR, APC-conjugated anti-CD3, Alexa fluor 488-conjugated anti-CD282 (TLR2), and PE-conjugated anti CD284 (TLR4). Lymphocytes were selected (R1) and then gated on CD3+ cells (R2) and HLA-DR+ cells (R3). R2 was further analyzed for TLR2 and TLR4 expression.
See this image and copyright information in PMC

References

    1. Wang ES. Common fungal infections in patients with leukemia. Clin Adv Hematol Oncol. 2017;15(5):352–4. - PubMed
    1. Heimann SM, Vehreschild MJ, Cornely OA, Franke B, von Bergwelt-Baildon M, Wisplinghoff H, et al. A cost and resource utilization analysis of micafungin bridging for hemato-oncological high-risk patients undergoing allogeneic stem cell transplantation. Eur J Haematol. 2015;94(6):526–31. doi: 10.1111/ejh.12466. - DOI - PubMed
    1. Rambaldi B, Russo D, Pagano L. Defining Invasive Fungal Infection Risk in Hematological Malignancies: A New Tool for Clinical Practice. Mediterr J Hematol Infect Dis. 2017;9(1):e2017012. doi: 10.4084/mjhid.2017.012. - DOI - PMC - PubMed
    1. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) Ann Hematol. 2017;96(11):1775–92. doi: 10.1007/s00277-017-3098-3. - DOI - PMC - PubMed
    1. DePauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) C. Clin Infect Dis. 2008;46(12):1813–21. doi: 10.1086/588660. - DOI - PMC - PubMed