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Autoimmune diseases, such as rheumatoid arthritis (RA), are examples of yet not entirely understood etiology. They are linked to immune system dysfunction, which becomes immunologically overactive, damaging the body’s tissues and organs. At least three major factors underlie the development of autoimmune disorders: environmental factors, including the oral and intestinal microbiomes, genetic predisposition, and aberrant autoimmune response. The dysbiosis of the oral microbiota, in particular, exerts a significant effect on RA, clinically manifested by damage of the joints. RA is significantly associated with periodontitis, which is caused by an increased abundance of Porphyromonas gingivalis in the subgingival niche, which disturbs the homeostasis of the oral microbial community. P. gingivalis is considered to contribute to the development and progression of RA. Although this bacterium may escape detection by the host immune system, it still induces an immune imbalance. RA and periodontitis also share similar pathological and clinical features. The progression of both chronic periodontitis and RA is linked to the dysregulation of the immune system and the damage caused by the immune response. Previous detailed studies have indicated that a specific enzyme of P. gingivalis, peptidyl-arginine deiminase, which catalyzes the citrullination of proteins, may trigger the autoimmune response resulting in the development of RA.

The larvae of the insect Galleria mellonella have gained wide acceptance as an in vivo model for the study of virulence in Gram-negative and Gram-positive bacteria and fungi. Importantly, G. mellonella offers an alternative, low-cost, and ethically acceptable method of assessing pathogens. These insects have a number of advantages, including ease of breeding, a rapid developmental cycle, low maintenance costs, and ease of experimental manipulation. Most importantly, G. mellonella larvae have a complete immune system and a nonspecific immune response similar to that of humans, making them a valuable model for studying pathogen-host interactions. Furthermore, using this model, it is possible to test the efficacy of various chemical compounds or natural substances that show antimicrobial activity. In this literature review, we provide a comprehensive overview of recent studies of the use of G. mellonella in virulence analyses and as a platform for testing the efficacy of new drugs.

Previous studies have demonstrated that hemoglobin (Hb) and bacterial endotoxin (lipopolysaccharide, LPS) form stable complexes and result in disaggregation of macromolecular LPS. To examine the effect of complex formation on LPS biological activity, we investigated the ability of Hb to alter LPS-induced activation of the coagulation cascade of Limulus amebocyte lysate (LAL) and expression of tissue factor from human endothelial cells. Both native HbAo and derivatized (covalently cross-linked) hemoglobin resulted in prominent enhancement of LAL activation and endothelial cell tissue factor production by Proteus mirabilis LPS. No substantial differences were observed between the enhancement effect of Hb on P. mirabilis smooth and rough LPS, indicating a dominant role for the lipid A component of LPS. Rough (Re) Salmonella minnesota 595 LPS also demonstrated both enhanced activation of LAL and stimulation of endothelial cell tissue factor in the presence of Hb. In contrast, neither lipid A nor singly dephosphorylated or partially deacylated Re LPS manifested significant enhancement of LAL activation by Hb, and partially deacylated Re LPS showed no enhancement of endothelial cell tissue factor by Hb. These results suggest that the Kdo moieties, as well as the phosphate residues and fatty acyl moieties of lipid A, may be involved in the interaction of Hb with LPS. Comparison of Hb with other endotoxin binding proteins for ability to cause enhancement of LPS biological activity demonstrated more prominent enhancement with lipopolysaccharide binding protein (LBP) than that observed with Hb, lesser enhancement with albumin, and no enhancement effect with IgG or transferrin. [ABSTRACT FROM PUBLISHER]