From Infection to Autoimmunity: S. pyogenes as a Model Pathogen

Abstract

Group A β-hemolytic Streptococcus (GAS) is a Gram-positive, coccoid-shaped bacterium that tends to grow in chains; it is a non-spore-forming, facultatively anaerobic, catalase-negative, aerobic bacterium. It is known to cause a wide range of infections in children, ranging from mild upper respiratory tract infections, such as pharyngitis, to severe invasive disease. GAS also notably triggers post-infectious immune sequelae, including acute poststreptococcal glomerulonephritis (APSGN), acute rheumatic fever (ARF), and rheumatic heart disease (RHD), which are major health burdens, especially in low-income countries. In this review, we will present the general characteristics of GAS, highlighting its structural and microbiological features. We will also discuss its pathogenetic mechanisms, especially molecular mimicry, and its ability to cause autoimmune responses. Finally, we will elucidate some of the autoimmune sequelae that mark GAS infections, such as ARF, RHD, APSGN, and guttate psoriasis. Understanding GAS as a model pathogen for infection-induced autoimmunity provides insight into host-pathogen interactions and supports the development of targeted interventions. Emphasis on early diagnosis and antibiotic treatment is essential to reduce the burden of autoimmune complications.

Keywords: acute post-streptococcal glomerulonephritis; acute rheumatic fever; autoimmune; group A streptococcus; guttate psoriasis; molecular mimicry; rheumatic heart disease.

Figure 1

Initial infection and colonization: GAS adheres to epithelial cells through fibronectin. This interaction seems to be mediated by protein F, considered the main adhesin of the bacterium.

Figure 2

Immune evasion and systemic spread. M protein is a fibrillar protein complexed with teichoic acids, such as lipoteichoic acid (LTA), and is crucial in the pathogenicity of the bacterium. It anchors to the cell membrane with the LPSTGE motif and interferes with opsonization, inhibiting the complement pathway by binding Factor H and fibrinogen, reducing the amount of C3b bound to streptococci. Moreover, GAS produces superantigenic molecules, which enhance its virulence, playing a critical role in severe invasive infections. Immune evasion is also fostered by superantigens, highly stimulating T-CD4+ and T-CD8+ cells, resulting in an uncontrolled stimulation of T-cells and, therefore, a massive release of proinflammatory cytokines. Furthermore, GAS evades phagocytosis by producing an NADase.

Figure 3

Post-infectious and autoimmune sequelae.