Bacterial infections in lupus: Roles in promoting immune activation and in pathogenesis of the disease

Abstract

Background: Bacterial infections of the lung, skin, bloodstream and other tissues are common in patients with systemic lupus erythematosus (lupus) and are often more severe and invasive than similar infections in control populations. A variety of studies have explored the changes in bacterial abundance in lupus patients, the rates of infection and the influence of particular bacterial species on disease progression, using both human patient samples and mouse models of lupus.

Objective: The aim of this review is to summarize human and mouse studies that describe changes in the bacterial microbiome in lupus, the role of a leaky gut in stimulating inflammation, identification of specific bacterial species associated with lupus, and the potential roles of certain common bacterial infections in promoting lupus progression.

Methods: Information was collected using searches of the Pubmed database for articles relevant to bacterial infections in lupus and to microbiome changes associated with lupus.

Results: The reviewed studies demonstrate significant changes in the bacterial microbiome of lupus patients as compared to control subjects and in lupus-prone mice compared to control mice. Furthermore, there is evidence supporting the existence of a leaky gut in lupus patients and in lupus-prone mice. This leaky gut may allow live bacteria or bacterial components to enter the circulation and cause inflammation. Invasive bacterial infections are more common and often more severe in lupus patients. These include infections caused by Staphylococcus aureus, Salmonella enterica, Escherichia coli, Streptococcus pneumoniae and mycobacteria. These bacterial infections can trigger increased immune activation and inflammation, potentially stimulating activation of autoreactive lymphocytes and leading to worsening of lupus symptoms.

Conclusions: Together, the evidence suggests that lupus predisposes to infection, while infection may trigger worsening lupus, leading to a feedback loop that may reinforce autoimmune symptoms.

Keywords: Feedback; Infection; Leaky gut; Microbiome; Systemic lupus erythematosus; Trigger.