Complement Inactivation Strategy of Staphylococcus aureus Using Decay-Accelerating Factor and the Response of Infected HaCaT Cells

Abstract

Staphylococcus aureus is a species of Gram-positive staphylococcus. It can cause sinusitis, respiratory infections, skin infections, and food poisoning. Recently, it was discovered that S. aureus infects epithelial cells, but the interaction between S. aureus and the host is not well known. In this study, we confirmed S. aureus to be internalized by HaCaT cells using the ESAT-6-like protein EsxB and amplified within the host over time by escaping host immunity. S. aureus increases the expression of decay-accelerating factor (CD55) on the surfaces of host cells, which inhibits the activation of the complement system. This mechanism makes it possible for S. aureus to survive in host cells. S. aureus, sufficiently amplified within the host, is released through the initiation of cell death. On the other hand, the infected host cells increase their surface expression of UL16 binding protein 1 to inform immune cells that they are infected and try to be eliminated. These host defense systems seem to involve the alteration of tight junctions and the induction of ligand expression to activate immune cells. Taken together, our study elucidates a novel aspect of the mechanisms of infection and immune system evasion for S. aureus.

AhR Activation Leads to Attenuation of Murine Autoimmune Hepatitis: Single-Cell RNA-Seq Analysis Reveals Unique Immune Cell Phenotypes and Gene Expression Changes in the Liver

“…In the current study, the use of scRNA-seq led to some surprising observations such as the changes occurring in the B cell compartment, especially CD55+ B cells, because ConA is a polyclonal T cell mitogen. CD55, also called Decay Accelerating Factor, is a regulatory protein involved in complement activation and has been shown to be modulated in many infections and diseases (66)(67)(68)(69). An increase in the surface expression of CD55 has been associated with inhibition of complement system activation (69).…”

“…CD55, also called Decay Accelerating Factor, is a regulatory protein involved in complement activation and has been shown to be modulated in many infections and diseases (66)(67)(68)(69). An increase in the surface expression of CD55 has been associated with inhibition of complement system activation (69). It has been reported that a decrease in the mean fluorescence intensity of CD55 was observed in T and B lymphocytes from systemic lupus erythematosus patients, implicating this marker as a possible player in lymphopenia (70).…”

Lipoteichoic Acid Isolated from Staphylococcus aureus Induced THP-1 Cell Apoptosis through an Autocrine Mechanism of Cytokines and SOCS-1-Mediated Bcl2 Inhibition

“…During infection, S. aureus induces apoptosis in a wide range of target cells as a means of invading tissues and antagonizing host immune defenses [22]. Cell death, such as apoptosis and necrosis, is also used when S. aureus is released from keratinocytes [23]. S. aureus produces apoptotic virulence factors, including potent toxins such as α-toxin and enterotoxins and superantigens [22].…”

The Role of the Oral Immune System in Oropharyngeal Candidiasis-Facilitated Invasion and Dissemination of Staphylococcus aureus

“…However, this is likely overcome during pathogenic candidal growth since the presence of C. albicans is known to significantly enhance the presence of S. aureus on the tongue of immunocompromised mice [ 10 , 11 , 13 ]. Similar to C. albicans, S. aureus has developed various mechanisms to avoid complement mediated killing, including the inhibition of MAC formation [ 100 ], inhibition of the classical and lectin pathways [ 101 ], and the utilization of various extracellular proteases which efficiently degrade crucial complement factors [ 102 ]. Since both organisms possess mechanisms to inhibit the complement system, their inhibitory potency likely adds up during co-infection.…”