Expression of HLA‐DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia

Abstract

To improve management of Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce dose-dependent immunosuppression that is evidenced by reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, the aim of this study was to determine whether expression of the MHC class II-related genes HLA-DRA and CD74 is more greatly reduced in complicated SAB, with its probable higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and blood samples taken on the day of confirmation of SAB (Day 1) and on Days 2, 3, 5 and 7. HLA-DRA and CD74 mRNA expression was determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification and SAB was categorized as complicated in patients with deep-seated infection and/or hematogenous seeding. Twenty patients with SAB were enrolled and samples obtained on all assessment days. HLA-DRA and CD74 expression did not differ significantly between patients with SAB and sepsis (n = 13) and those without sepsis (n = 7) on any assessment day. However, patients with complicated SAB (n = 14) had significantly weaker HLA-DRA expression on all five assessment days than patients with uncomplicated SAB (n = 6). Additionally, they tended to have weaker CD74 expressions. Neutrophil, monocyte and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB show weaker HLA-DRA expression than those with uncomplicated SAB during the first week of bacteremia.

Caspase‐1 inflammasome activity in patients with Staphylococcus aureus bacteremia

“…A suppressed immune response involving downregulated mRNA expression of NLRP1 accompanied by normal levels of IL1B and CASP1 mRNAs has been observed in ex vivo stimulated monocytes in patients with trauma, and reduced NLRP3 gene expression in patients suffering polytrauma has also been discussed . In addition, the patients with complicated SAB in the present study displayed downregulated mRNA levels of the immunosuppression marker human leucocyte antigen‐DRA, HLA‐DRA , recently shown by our group, indicating an immunocompromised state …”

Generation and expression analysis of BAC humanized mice carrying HLA‐DP401 haplotype

“…In vitro studies have shown that S aureus can reduce the expression of major histocompatibility complex (MHC) class II on antigen presenting cells 59 . The expression of the MHC class II‐related genes HLA‐DRA and CD74 is significantly reduced in complicated S aureus bacteremia (SAB) than in uncomplicated SAB, indicating that there is an association between complicated SAB and reduced MHC class II expression 60 . It is not clear yet why the HLA‐DP expression upregulated in thymus after S aureus infection.…”

Immunomonitoring of Monocyte and Neutrophil Function in Critically Ill Patients: From Sepsis and/or Trauma to COVID-19

“…They concluded that decreased CD74 mRNA expression significantly predicted 28-day mortality following septic shock. Expression of the MHC class II-related genes HLA-DRA and CD74 was investigated in patients with complicated and uncomplicated Staphylococcus aureus bacteremia (SAB) [219]. The complicated SAB group included patients with hematogenous seeding or extension of infection beyond the primary focus, etc.…”