Our finding that CCL3 inhibition enhances pathology is similar to the finding that in a model of nephritis CCR1−/− (the main receptor for CCL3) mice have enhanced pathology associated with increased TNF levels [16].
Collectively, the observation of the role of the CTLA4 −6230 polymorphism and the occurrence of a haplotype/diplotype bearing the CTLA4A variant in pulmonary TB indicates that a reduced CTLA-4 activity in humans does not enhance protection against pulmonary TB but enhances pathology if containment of the infection fails.
C5L2 stimulation by C5a caused release from cells of the protein high mobility group box 1 (HMGbothboth in vitro and in vivo and enhanced pathology in sepsis models [ 74].
Subsequently, and supportive of this hypothesis, transthyretin protein was shown to prevent Aβ toxicity in vitro [24,25] and in mice over-expressing APP, neutralisation with antibody or deletion of the TTR gene both enhance pathology [26,27].
However, the treatment of mice with anti-Tim-3 and anti-PD-1 neutralization antibodies did significantly enhance pathologies in the upper genital tract, demonstrating that the antibody treatment was effective in blocking of Tim-3 and PD-L1 signaling pathways.
These findings point to the need for serious consideration of whether environmental PPARγ ligands (e.g., TPP, phthalates, organotins) also have detrimental effects on bone health by accelerating osteoporosis or enhancing osteoporotic pathology.
Recently, BECN1 deficiency was shown to enhance the pathology of a mouse model of Alzheimer Disease ADD).
Whereas C57BL/6J mice could control virus replication and clear the infection, DBA/2J mice exhibited higher viral loads, higher levels of cytokines and chemokines, enhanced lung pathology, and were not able to clear the viral infection.
From a mechanistic perspective, insulin resistance may enhance cardiac pathology following a MI by inhibiting changes in metabolic characteristics that are initially suggested to be adaptive [ 26- 30].
MARCO knockout mice have been shown to be more susceptible to pneumococcal pneumonia, which was associated with higher bacterial loads, enhanced lung pathology and increased mortality rates [ 63].
