Inflammatory responses to migrating Brugia pahangi third-stage larvae - PubMed (original) (raw)

Inflammatory responses to migrating Brugia pahangi third-stage larvae

Kristina H Porthouse et al. Infect Immun. 2006 Apr.

Abstract

Despite being central to parasite establishment and subsequent host pathological and immunologic responses, host-parasite interactions during early third-stage filarial larva (L3) migration are poorly understood. These studies aimed to define early tissue migration of Brugia pahangi L3 in the gerbil (Meriones unguiculatus) and measure host cellular responses during this period. Gerbils were intradermally inoculated in the hind limb with 100 B. pahangi L3, and necropsies were performed at various times. At 3 h, most L3 (96.3%) were recovered from tissues associated with the infection site, with marked L3 migration occurring by 24 h. Larvae were dispersed throughout the lymphatics at 7 days postinfection (dpi), and at 28 dpi, most parasites were recovered from the spermatic cord lymphatics. Parasites were identified histologically at all time points. Inflammatory cells, primarily neutrophils, were frequently observed around larvae in the dermis and muscle near the injection site at 3 h and 24 h. Levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha mRNA peaked at 3 h in all tissues, with IL-6 levels also high in the spleen at 28 dpi. Levels of IL-4 mRNA were elevated in all tissues at 28 dpi. These observations demonstrate that L3 migrate quickly through various tissues and into lymph nodes in a predictable pattern. Migrating L3 induce an early acute inflammatory response that is modulated as parasites establish in the lymphatics. Polarization of the host response towards a dominant Th2-like profile is present at 7 dpi and is well established by 28 dpi in this permissive host.

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Figures

FIG. 1.

FIG. 1.

Histologic sections of Brugia pahangi L3 in various tissues during early migration. The bars shown indicate a size of 50 μm. (A) Larvae in the dermis of the left hind limb of a gerbil 3 h after i.d. infection with 100 B. pahangi L3. The arrow indicates inflammatory infiltrate surrounding the larvae that consists primarily of neutrophils with lesser numbers of eosinophils, basophils, and mononuclear cells. (B) Brugia pahangi larvae within a deep dermal lymphatic vessel of a gerbil 3 days after i.d. infection with 100 B. pahangi L3. Arrows indicate larvae within the lymphatic vessel. (C) Larvae in the subcapsular sinus of the left popliteal lymph node of a gerbil 7 days after i.d. infection with 100 B. pahangi L3. Arrows indicate larvae within the nodal sinus. No significant inflammation was apparent within the lymph node.

FIG. 2.

FIG. 2.

Quantitation of IL-6 mRNA in spleens (A), renal lymph nodes (LN) (B), and popliteal lymph nodes (C). Gerbils were necropsied at 3 h, 24 h, 3 days, 7 days, and 28 days after i.d. inoculation with Brugia pahangi L3. mRNA levels were measured by reverse transcription (RT)-PCR, and values are expressed as mean severalfold changes compared with values from control animals. Superscript letters indicate statistical significance (P < 0.05). Values with the same letter are not statistically different.

FIG. 3.

FIG. 3.

Quantitation of TNF-α mRNA in spleens (A), renal lymph nodes (LN) (B), and popliteal lymph nodes (C). Gerbils were necropsied at 3 h, 24 h, 3 days, 7 days, and 28 days after i.d. inoculation with Brugia pahangi L3. mRNA levels were measured by RT-PCR, and values are expressed as the mean severalfold changes compared with values from control animals. Superscript letters indicate statistical significance (P < 0.05). Values with the same letter are not statistically different. No statistically significant differences were found in the spleen (P = 0.065) or popliteal lymph node (P = 0.2).

FIG. 4.

FIG. 4.

Quantitation of IFN-γ mRNA in spleens (A), renal lymph nodes (LN) (B), and popliteal lymph nodes (C). Gerbils were necropsied at 3 h, 24 h, 3 days, 7 days, and 28 days after i.d. inoculation with B. pahangi L3. mRNA levels were measured by RT-PCR, and values are expressed as mean severalfold changes compared with values from control animals. Superscript letters indicate statistical significance (P < 0.05). Values with the same letter are not statistically different. No statistically significant differences were found in the renal lymph nodes (P = 0.094).

FIG. 5.

FIG. 5.

Quantitation of IL-4 mRNA in spleens (A), renal lymph nodes (LN) (B), and popliteal lymph nodes (C). Gerbils were necropsied at 3 h, 24 h, 3 days, 7 days, and 28 days after i.d. inoculation with B. pahangi L3. mRNA levels were measured by RT-PCR, and values are expressed as the mean severalfold changes compared with values from control animals. Superscript letters indicate statistical significance (P < 0.05). Values with the same letter are not statistically different.

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References

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