Gut Leakage of Fungal‐Related Products: Turning Up the Heat for HIV Infection

Abstract

The intestinal epithelial layer serves as a physical and functional barrier between the microbiota in the lumen and immunologically active submucosa. Th17 T-cell function protects the gut epithelium from aggression from microbes and their by-products. Loss of barrier function has been associated with enhanced translocation of microbial products which act as endotoxins, leading to local and systemic immune activation. Whereas the inflammatory role of LPS produced by Gram-negative bacteria has been extensively studied, the role of fungal products such as β-D-glucan remains only partially understood. As HIV infection is characterized by impaired gut Th17 function and increased gut permeability, we critically review mechanisms of immune activation related to fungal translocation in this viral infection. Additionally, we discuss markers of fungal translocation for diagnosis and monitoring of experimental treatment responses. Targeting gut barrier dysfunction and reducing fungal translocation are emerging strategies for the prevention and treatment of HIV-associated inflammation and may prove useful in other inflammatory chronic diseases.

Aging With Grace for People Living With HIV: Strategies to Overcome Leaky Gut and Cytomegalovirus Coinfection

“… 5 , 17 , 18 These findings suggest that BDG is originating from the gut. 16 Moreover, BDG levels were associated with inflammation markers, including proinflammatory cytokines, markers of myeloid cell activation, neopterin levels, and tryptophan metabolism in PLWH. 5 , 16 , 19 , 20 Although the association of BDG with gut damage and microbial translocation–associated inflammation were found by several studies in PLWH, the gut origin of these fungal products remain correlative.…”

“… 16 Moreover, BDG levels were associated with inflammation markers, including proinflammatory cytokines, markers of myeloid cell activation, neopterin levels, and tryptophan metabolism in PLWH. 5 , 16 , 19 , 20 Although the association of BDG with gut damage and microbial translocation–associated inflammation were found by several studies in PLWH, the gut origin of these fungal products remain correlative. Strategies used in animal models to confirm the gut origin of translocation LPS in SIV-infected macaques could be used in future studies.…”

“… 16 In absence of invasive fungal infection, BDG plasma levels have been evaluated as a possible fungal translocation marker in PLWH. 16 …”

Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

“…Damage to the gastrointestinal epithelial gut barrier and subsequent translocation of microbes and their byproducts in the circulation constitute hallmarks of HIV infection and participate in systemic inflammation during chronic HIV infection [ 28 , 34 , 35 ]. The exact mechanisms responsible for gut damage and epithelial permeability are not fully understood, and these alterations do not improve upon ART initiation.…”

Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review

“…BDG is a component of the cell wall of fungi, and identification of plasma BDG is currently used for the clinical diagnosis of invasive fungal infections (124). Morris et al reported that high serum levels of BDG are associated with a decrease of CD4 + T-cell counts, a higher viral load, and activation of CD8 + T-cells in PLWH (125,126). Intestinal fatty acid binding protein (I-FABP), expressed in enterocytes, is released upon cell death, and enters into the systemic circulation (127).…”