How to Get Away from the Immune System

From manipulating host molecules to concealing their presence in the host’s body, microbes employ a wide range of tactics to dodge immune detection.

Written byMariella Bodemeier Loayza Careaga, PhD

| 3 min read

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The immune system is highly trained to detect and eliminate any potential threat to the human body. While years of evolution have turned this system into a pathogen-killing machine, the microbes it fights have also evolved intricate strategies to evade it.

A Parasite and the Art of Cloaking

On the left, several red blood cells are shown sticking to blood vessel walls, with grey malaria parasites within them. On the right, a graph shows how parasitemia rises and falls over time as the parasite uses different forms of PfEMP1.

modified from © istock.com, Shivendu Jauhari, Irfan Setiawan, Eranicle

1) The malaria parasite Plasmodium falciparum expresses the protein PfEMP1 on the surface of erythrocytes to adhere the cells to blood vessel walls and escape clearance by the spleen.

2) PfEMP1 can be detected by immune cells. Through the process of antigenic variation, P. falciparum expresses different versions of it and escapes immune recognition.

Controlling the Enemy Within

On the left, Mycobacterium tuberculosis bacteria enter a macrophage and pathways by which the bacteria avoid destruction, and how they disrupt communication between the macrophage and a T cell (shown on the right) are depicted.

modified from © istock.com, ttsz

3) Inside macrophages, Mycobacterium tuberculosis dodges intracellular degradation by secreting virulence factors. Two effectors, EsxH and EsxG, inhibit the function of the ESCRT machinery, impairing the maturation of bacteria-carrying phagosomes.

4) Another Mycobacterium virulence factor, CpsA, disrupts another degradation pathway and blocks the activity of NADPH oxidase, impairing the destruction of the bacteria.

5) By affecting the normal function of ESCRT, M. tuberculosis EsxH-EsxG complex also disturbs the process of antigenic presentation via the MHC-II molecule.

A Viral Manipulator

On the left, HIV disrupts surface expression of MHC proteins in a T cell; HIV also impairs communication between T cells and an antigen-presenting cell, shown on the right.

modified from © istock.com, ttsz, bombuscreative

6) To stay hidden inside lymphocytes, HIV-1 expresses viral factors such as the negative factor (Nef) protein. In the infected cell, Nef downregulates the expression of MHC-I and MHC-II on the cell surface, impairing the presentation of viral antigens.

7) Nef also disrupts the proper formation of immunological synapses, the points of communication between T cells and antigen-presenting cells.

A Temporary Fungal Shield

on the left, a pink Candida albicans cell is shown. A section of the cell wall is enhanced to show how the beta-glucans, shown in green, are covered by mannans, shown in blue. On the right, macrophages recognize beta-glucans.

8) In Candida albicans, beta-glucans are a major target for immune detection by macrophages, which are one of the first lines of immune defense. The fungus covers its beta-glucans with a layer of mannans, shielding them from macrophage detection to prolong their stay in the host.

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References

Deitsch KW, Dzikowski R. Variant gene expression and antigenic variation by malaria parasites. Annu Rev Microbiol. 2017;71:625-641.
Chandra P, et al. Immune evasion and provocation by Mycobacterium tuberculosis. Nat Rev Microbiol. 2022;20(12):750-766.
Fackler OT, et al. Modulation of the immunological synapse: A key to HIV-1 pathogenesis?. Nat Rev Immunol. 2007;7(4):310-317.
Gow NAR, Lenardon MD. Architecture of the dynamic fungal cell wall. Nat Rev Microbiol. 2023;21(4):248-259.
Gilbert AS, et al. Fungal pathogens: Survival and replication within macrophages. Cold Spring Harb Perspect Med. 2014;5(7):a019661.

Meet the Author

Mariella Bodemeier Loayza Careaga, PhD

Mariella joined The Scientist in 2023. Before that, she was a postdoctoral researcher at the Uniformed Services University of the Health Sciences studying sex differences on the effects of chronic stress and traumatic brain injury. Mariella holds a master’s and a PhD in neuroscience from the Universidade Federal de Sao Paulo, Brazil, and a certificate in Science Communication from the University of California, San Diego.

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