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regulate the function of interferon-γ in T-cell and natural Pryoptosis and infection diseases in the nervous system
killer cell. [27,28] Finally, they can recruit and activate Pyroptosis and its related molecules may participate
other immune cells and induce the synthesis of other in the development of nervous system encephalitis
inflammatory cytokines, chemokines, and adhesion and meningitis. These phenomena have a different
molecules, expanding local inflammation response. [13] prognosis in bacterial and virus infection. For
Moreover, cell membrane integrity is destroyed by example, in Streptococcus pneumoniae meningitis
micro-pores formation on it, which is caused by participation of NLRP3 inflammasome aggravate the
caspase-1, IL-1β and IL-18. These micro-pores lead to a damage caused by the disease. IL-1β and IL-18 are
series of pyroptoic processes such as cytoplasm release, not involved in growth inhibition of bacteria, but
cell osmotic lysis and inflammatory reaction. [13,29] In contribute to exacerbate the inflammatory response
addition, during the process of the pyroptosis, caspase-1 in the nervous system. [47-49] Some studies indicate
is involved in chromosomes and DNA degradation. that mouse microglia and peripheral macrophages
A specific endonuclease is activated by caspase-1. Once infected with Staphylococcus aureus, Mycobacterium
activated, this endonuclease can mediate degradation tuberculosis and Legionella pneumophila in vitro may
of DNA, which differs from the DNA degradation activate the NLRP3 or NLRP4 inflammasome thus
occurring in apoptosis. [29] More experiments have inducing pyroptosis. [32,50,51]
confirmed that the degradation of cytoskeletal proteins
is also associated with pyroptosis and that this process However, in viral encephalitis caused by West Nile
is related with treatment and processing of substrates virus (WNV), influenza A virus, and herpes simplex
by caspase-1. [30] virus, IL-1β and IL-18 can increase survival rate
of neurons by inhibiting viremia. [39,52-54] In WNV
PYROPTOSIS AND NEUROLOGICAL DISEASES encephalitis, it was observed that the production
and release of IL-1β increased in neurons, and IL-1β
Pyroptosis is closely related to neurological diseases. inhibited the replication of WNV. The survival rate
Pyroptosis and its relative mechanisms participate decreased in NLRP3 and ASC knockout mice infected
in acute and chronic aseptic inflammation in the by WNV. ASC knockout mice can experience excessive
nervous system. Our immune system could recognize immune response after WNV infection, and this will
disease-associated molecules through PRR. In the contribute to neuronal damage. Japanese encephalitis
[39]
central nervous system (CNS), PRR are expressed virus can activate NLRP3 inflammasome in microglia,
mainly on microglial, macrophages and astrocytes. promote the release of IL-1β and IL-18. [34] In CMV
They are distributed on the surface of membranes to retinitis, it was also observed microglia death through
recognize extracellular signals (i.e. toll like receptors), pyroptosis pathway. [55] But their influence on prognosis
or in the cytoplasm to transmit intracellular signal is not yet clear.
(i.e. NLR receptor).
Pyroptosis and acute aseptic disease in the nervous system
There are several NLRP1 and NLRP3 inflammasomes In acute aseptic nervous system damage (such as stroke or
expressed in the nervous system. [31] Mouse microglial traumatic brain injury), local autoimmune activation can
cells could express NLRP3 and NLRP4 inflammasome, cause nerve injury. Studies have demonstrated that mice
and they can respond to stimulation of dangerous with caspase-1 defection may have a certain resistance to
signals. [32-35] Additional evidences indicate that stroke, which indicated that pyroptosis and its relative
inflammasomes can be expressed in nonmyeloid cells mechanisms exacerbate brain damage in stroke. IL-18
[56]
of the nervous system. Meanwhile, many studies have knockout mice didn’t show any kind of protective effects
proven that caspase-1, IL-1β and IL-18 could be activated in stroke. In contrast, some IL-1 receptor antibodies
and NLRs inflammasomes can be assembled in neurons could still have a protective effect(s) to neurons, even
under stress conditions. [36-40] In addition, recent studies after the occurrence of stroke. This suggests that the
have also shown that NLRP2 inflammasomes can be protective effect is not only dependent on IL-1β, but
expressed in astrocytes. [41,42] In the CNS, microglia, also IL-1α. IL-1β and IL-1α defected mice have a better
astrocytes and neurons can all undergo pyroptosis resistance to stroke. Although IL-1α and caspase-1 do
[57]
and express its related downstream molecules and not have a direct relationship, caspase-1 may have an
receptors, thus taking part in the immune reaction to indirect protective effect (s) by influencing IL-1R2 and
local inflammation. [27,28,43] In fact, in diseases such as caspase-1 dependent nonclassical secretion system. [58,59]
viral encephalitis, stroke, Alzheimer’s disease (AD) Meanwhile, inflammasome also been observed in a
and multiple scleroses (MS), many studies have shown study of excitotoxic injury in kainate model. [38]
massive expression of IL-1β and IL-18 etc., in the
nervous system. [39,44-46] However, further investigation Similarly, in the rodent model, antibodies for ASC or
is required to elucidate mechanisms. NLRP1 can reduce injury of brain trauma or stroke. [60,61]

62 Neuroimmunol Neuroinflammation | Volume 1 | Issue 2 | September 2014