The innate immune response during urinary tract infection and pyelonephritis

Abstract

Despite its proximity to the fecal flora, the urinary tract is considered sterile. The precise mechanisms by which the urinary tract maintains sterility are not well understood. Host immune responses are critically important in the antimicrobial defense of the urinary tract. During recent years, considerable advances have been made in our understanding of the mechanisms underlying immune homeostasis of the kidney and urinary tract. Dysfunctions in these immune mechanisms may result in acute disease, tissue destruction and overwhelming infection. The objective of this review is to provide an overview of the innate immune response in the urinary tract in response to microbial assault. In doing so, we focus on the role of antimicrobial peptides – a ubiquitous component of the innate immune response.

Innate Immune Response to Urinary Tract Infections Involving Escherichia coli

“…HPNs encounter bacteria either when the phagocytic vacuole fuses with the HPN, or after being secreted. The HPNs provide non-oxidative antimicrobial activity [14]. The β-defensins are expressed constitutively in epithelial cells.…”

“…Complement components functions in opsonization of microorganisms and produce pores in the outer membrane of the bacteria causing leaking of cell contents [43,44]. IL-6 may activate B cells resulting in production of secretory IgA (sIgA) and stimulation of production of C-reactive protein, which further encourages the inflammatory cascade [14].…”

The multiple antibacterial activities of the bladder epithelium

“…These receptors are wired to distinct signaling circuits which activate multiple antimicrobial activities within and outside these superficial epithelial cells. Although the antimicrobial peptides β-defensin 1 and cathelicidin are constitutively secreted by BECs, their level of expression is greatly enhanced upon activation of TLR4 and other receptors (16)(17)(18)(19). These bactericidal peptides work by intercalating into and disrupting bacterial membranes (18), which is especially effective in limiting the survival of prospective pathogens in the early phase of infection and they represent one of the earliest extracellular antimicrobial responses mediated by epithelial cells (17).…”

“…Concurrent with the enhanced secretion of antimicrobial peptides by superficial BECs is secretion of multiple chemokines and pro-inflammatory cytokines. The chemokines include CXCL1 (20) and , and the early pro-inflammatory cytokines include IL-1β, IL-6 and TNF (14,19). Many of the cytokines are released via a canonical NF-κB pathway mediated by the adaptor MyD88 (14), while a rapid IL-6 response (22) appears to be mediated by a non-canonical cAMP pathway involving Ca 2+ flux and the cAMP response element-binding (CREB)…”

Influence of Bestim Immunomodulator on Immune Status and Free-Radical Oxidation in Patients With Chronic Pyelonephritis Associated With Urolithiasis

“…зависит от эффективности работы механизмов врожден-ного и адаптивного иммунитета, регуляции реакций воспалительного процесса. В послед-ние годы достигнуты значительные успехи в понимании механизмов иммунного гомеоста-за почек и мочевыводящих путей при инфек-ционном поражении [21]. Активно обсуждает-ся роль факторов иммунной системы в патоге-незе осложнений при МКБ.…”