Organic Matrix Derived from Host–Microbe Interplay Contributes to Pathological Renal Biomineralization

Matrix stones are a rare form of kidney stones. They
feature a
high percentage of hydrogel-like organic matter, and their formation
is closely associated with urinary tract infections. Herein, comprehensive
materials and biochemical approaches were taken to map the organic–inorganic
interface and gather insights into the host–microbe interplay
in pathological renal biomineralization. Surgically extracted soft
and slimy matrix stones were examined using micro-X-ray computed tomography
and various microspectroscopy techniques. Higher-mineral-density laminae
were positive for calcium-bound Alizarin red. Lower-mineral-density
laminae revealed periodic acid-Schiff-positive organic filamentous
networks of varied thickness. These organic filamentous networks,
which featured a high polysaccharide content, were enriched with zinc,
carbon, and sulfur elements. Neutrophil extracellular traps (NETs)
along with immune response-related proteins, including calprotectin,
myeloperoxidase, CD63, and CD86, also were identified in the filamentous
networks. Expressions of NETs and upregulation of polysaccharide-rich
mucin secretion are proposed as a part of the host immune defense
to “trap” pathogens. These host−microbe derived
organic matrices can facilitate heterogeneous nucleation and precipitation
of inorganic particulates, resulting in macroscale aggregates known
as “matrix stones”. These insights into the plausible
aggregation of constituents through host–microbe interplay
underscore the unique “double-edged sword” effect of
the host immune response to pathogens and the resulting renal biominerals.