Editing Toxoplasmosis (section)

===Parasitology===
In its lifecycle, ''T. gondii'' adopts several forms.<ref name="Robert-GangneuxDarde2012"/> [[Tachyzoites]] are responsible for acute infection; they divide rapidly and spread through the tissues of the body. Tachyzoites are also known as "tachyzoic merozoites", a descriptive term that conveys more precisely the parasitological nature of this stage.<ref>{{cite journal|last1=Markus|first1=MB|title=Terms for coccidian merozoites|journal=Annals of Tropical Medicine and Parasitology|date=1987|volume=81|issue=4|pages=463|doi=10.1080/00034983.1987.11812147|pmid=3446034}}</ref> After proliferating, tachyzoites convert into [[bradyzoites]], which are inside latent intracellular tissue [[cyst]]s that form mainly in the muscles and brain. The formation of cysts is in part triggered by the pressure of the host immune system.<ref name=Miller2009/> The bradyzoites (also called "bradyzoic merozoites") are not responsive to antibiotics. Bradyzoites, once formed, can remain in the tissues for the lifespan of the host. In a healthy host, if some bradyzoites convert back into active tachyzoites, the immune system will quickly destroy them. However, in immunocompromised individuals, or in fetuses, which lack a developed immune system, the tachyzoites can run rampant and cause significant neurological damage.<ref name="Robert-GangneuxDarde2012"/>

The parasite's survival is dependent on a balance between host survival and parasite proliferation.<ref name=Miller2009>{{cite journal|author1=Miller CM|author2=Boulter NR|author3=Ikin RJ|author4=Smith NC|title=The immunobiology of the innate response to ''Toxoplasma gondii''|journal=International Journal for Parasitology|date=January 2009|volume=39|issue=1|pages=23–39|doi=10.1016/j.ijpara.2008.08.002|pmid=18775432}}</ref> ''T.&nbsp;gondii'' achieves this balance by manipulating the host's immune response, reducing the host's immune response, and enhancing the parasite's reproductive advantage.<ref name=Miller2009 /> Once it infects a normal host cell, it resists damage caused by the host's immune system, and changes the host's immune processes.<ref>{{cite journal |last1=Brasil |first1=Thaís Rigueti |last2=Freire-de-Lima |first2=Celio Geraldo |last3=Morrot |first3=Alexandre |last4=Vetö Arnholdt |first4=Andrea Cristina |title=Host-Toxoplasma gondii Coadaptation Leads to Fine Tuning of the Immune Response |journal=Frontiers in Immunology |date=2017 |volume=8 |page=1080 |doi=10.3389/fimmu.2017.01080 |pmid=28955329 |pmc=5601305 |doi-access=free }}</ref>
As it forces its way into the host cell, the parasite forms a [[parasitophorous vacuole]] (PV) membrane from the membrane of the host cell.<ref name=Hunter2012>{{cite journal|last1=Hunter|first1=CA|last2=Sibley|first2=LD|title=Modulation of innate immunity by ''Toxoplasma gondii'' virulence effectors|journal=Nature Reviews Microbiology|date=November 2012|volume=10|issue=11|pages=766–78|doi=10.1038/nrmicro2858|pmid=23070557|pmc=3689224}}</ref><ref name=Martens2005>{{cite journal|author1=Martens S|author2=Parvanova I|author3=Zerrahn J|author4=Griffiths G|author5=Schell G|author6=Reichmann G|author7=Howard JC|title=Disruption of ''Toxoplasma gondii'' parasitophorous vacuoles by the mouse p47-resistance GTPases |journal=PLOS Pathogens |date=November 2005 |volume=1 |issue=3 |pages=e24 |doi=10.1371/journal.ppat.0010024 |pmid=16304607|pmc=1287907 |doi-access=free }}</ref> The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host's [[mitochondria]] and [[endoplasmic reticulum]].<ref name=Hunter2012 /><ref name=Martens2005 />

When first invading the cell, the parasite releases ROP proteins from the bulb of the [[rhoptry]] organelle.<ref name=Hunter2012 /> These proteins translocate to the nucleus and the surface of the PV membrane where they can activate [[STAT protein|STAT]] pathways to modulate the expression of [[cytokine]]s at the transcriptional level, bind and inactivate PV membrane destroying [[IRGs|IRG]] proteins, among other possible effects.<ref name=Hunter2012 /><ref name=Martens2005 /><ref name=Denkers2012>{{cite journal |last1=Denkers |first1=Eric Y. |last2=Schneider |first2=Anne G. |last3=Cohen |first3=Sara B. |last4=Butcher |first4=Barbara A. |title=Phagocyte Responses to Protozoan Infection and How Toxoplasma gondii Meets the Challenge |journal=PLOS Pathogens |date=2 August 2012 |volume=8 |issue=8 |pages=e1002794 |doi=10.1371/journal.ppat.1002794 |pmid=22876173 |pmc=3410898 |doi-access=free }}</ref> Additionally, certain strains of ''T.&nbsp;gondii'' can secrete a protein known as GRA15, activating the [[NF-κB]] pathway, which upregulates the pro-inflammatory [[cytokine]] [[Interleukin 12|IL-12]] in the early immune response, possibly leading to the parasite's latent phase.<ref name=Hunter2012 /> The parasite's ability to secrete these proteins depends on its genotype and affects its virulence.<ref name=Hunter2012 /><ref name=Denkers2012 />

The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of [[apoptosis]] resistance is by disrupting pro-apoptosis effector proteins, such as [[Bcl-2-associated X protein|BAX]] and [[Bcl-2 homologous antagonist killer|BAK]].<ref name="Hippe_2009">{{cite journal |vauthors=Hippe D, Weber A, Zhou L, Chang DC, Häcker G, Lüder CG | title = ''Toxoplasma gondii'' infection confers resistance against Bim<sub>S</sub>-induced apoptosis by preventing the activation and mitochondrial targeting of pro-apoptotic Bax | journal = Journal of Cell Science | volume = 122 | issue = Pt 19 | pages = 3511–21 | year = 2009 | pmid = 19737817 | doi = 10.1242/jcs.050963 | doi-access = free }}</ref> To disrupt these proteins, ''T.&nbsp;gondii'' causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. ''T.&nbsp;gondii'' does not, however, cause downregulation of the pro-apoptosis effector proteins.<ref name="Hippe_2009" />

''T. gondii'' also has the ability to initiate [[autophagy]] of the host's cells.<ref name="Wang">{{cite journal |vauthors=Wang Y, Weiss LM, Orlofsky A | title = Host cell autophagy is induced by ''Toxoplasma gondii'' and contributes to parasite growth | journal = The Journal of Biological Chemistry | volume = 284 | issue = 3 | pages = 1694–701 | year = 2009 | pmid = 19028680 | pmc = 2615531 | doi = 10.1074/jbc.M807890200 | doi-access = free }}</ref> This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang ''et al'' finds that infected cells lead to higher levels of autophagosomes in normal and infected cells.<ref name="Wang" /> Their research reveals that ''T.&nbsp;gondii'' causes host cell autophagy using a calcium-dependent pathway.<ref name="Wang" /> Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells.<ref name="Hippe_2009" />

The mechanisms above allow ''T.&nbsp;gondii'' to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of ''T.&nbsp;gondii'' per host cell cause a more severe effect.<ref name="Laliberte_2008">{{cite journal |vauthors=Laliberté J, Carruthers VB | title = Host cell manipulation by the human pathogen ''Toxoplasma gondii'' | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 12 | pages = 1900–15 | year = 2008 | pmid = 18327664 | pmc = 2662853 | doi = 10.1007/s00018-008-7556-x }}</ref> The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals.<ref name="Laliberte_2008" />

''T. gondii'' has been shown to produce a protein called GRA28, released by the MYR1 secretory pathway, which interferes with gene expression in infected cells and results in cells that behave like dendritic cells, becoming highly mobile in the body.<ref>{{cite journal |last1=ten Hoeve |first1=Arne L. |last2=Braun |first2=Laurence |last3=Rodriguez |first3=Matias E. |last4=Olivera |first4=Gabriela C. |last5=Bougdour |first5=Alexandre |last6=Belmudes |first6=Lucid |last7=Couté |first7=Yohann |last8=Saeij |first8=Jeroen P.J. |last9=Hakimi |first9=Mohamed-Ali |last10=Barragan |first10=Antonio |title=The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages |journal=Cell Host & Microbe |date=November 2022 |volume=30 |issue=11 |pages=1570–1588.e7 |doi=10.1016/j.chom.2022.10.001 |pmc=9710525 |pmid=36309013 }}</ref>

Since the parasite can change the host's immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats.<ref name=Miller2009 /> This includes, but is not limited to, the responses to infections by ''[[Helicobacter felis]]'', ''[[Leishmania major]]'', or other parasites, such as ''[[Nippostrongylus brasiliensis]]''.<ref name=Miller2009 />